Torrey Pines Institute for Molecular Studies science image
Torrey Pines Institute for
Molecular Studies

3550 General Atomics Court, 2-129
San Diego, CA 92121-1122
USA
Scientists
Richard A. Houghten
President

858.455.3803 - phone
858.455.3804 - fax

Founder

Richard A. Houghten, is the founder and President of Torrey Pines Institute for Molecular Studies. The Institute was founded in 1988, and began its operations in 1989 with eight employees. Now in its 17th year, it has become internationally recognized for its scientific contributions in a wide range of fields, including chemistry, multiple sclerosis, diabetes, immunology, infectious disease, heart disease, cancer vaccines and pain management. The institute has grown to include over 75 scientists, technicians and administrative staff, all of whom work in an environment that emphasizes personal and professional growth by encouraging the development of independent research ideas as well as the development of collaborative efforts with scientists throughout the world.

Dr. Houghten received his doctorate in organic chemistry from the University of California, Berkeley, in 1975. Following positions at the University of California, San Francisco, and Mount Sinai School of Medicine, he joined The Scripps Research Institute in 1981. In addition to Torrey Pines Institute for Molecular Studies, he founded three commercial businesses, including one which became a publicly-traded biotechnology company.

His achievements have been recognized in the form of numerous honors and awards. Most recently, his contributions to the field of combinatorial chemistry and peptide science was acknowledged by the Bruce Merrifield Award in 2005. Just one year prior, he was awarded the 2004 Ralph F. Hirschmann Award in Peptide Chemistry by the American Chemical Society. Other honors received include the Vincent du Vigneaud Award for Excellence in Peptide Science (2000) and the UCSD Connect Athena Pinnacle Award for Empowering Women in the Workplace. His acceptance of the Athena Pinnacle Award in 1999 further distinguishes Dr. Houghten and his dedication to the mentoring and advancement of women scientists in the work place.

Dr. Houghten’s scientific contributions include the “tea bag” approach, which was originally utilized to facilitate the synthesis of peptides in 1985. The tea bag method, in which solvent permeable packets are used during the synthesis process, has now resulted in not only the synthesis of millions of peptides, but also the synthesis of millions of low molecular weight compounds.

In collaboration with his long time associates and colleagues at Torrey Pines Institute for Molecular Studies, he developed approaches in combinatorial chemistry which are invaluable for the rapid identification of individual compounds from millions to billions of others (positional scanning), the use of existing combinatorial libraries to generate entirely new diversities of compounds (libraries from libraries), the cross-referencing of library screening results with gene data bases in order to fine-tune the direction towards which further testing moves for a given disease target (biometrical analysis), and novel volatilizable solid supports. Many of these technologies have resulted in “leads”, which are today undergoing further testing and analysis in pharmaceutical companies.

Publications

  1. Hoesl, C.E., Ostresh, J.M., Houghten, R.A., Nefzi, A. Solid phase synthesis of 3,4,7-trisubstituted 4,5,8,9-tetrahydro-3H-imidazo[1,2-a][1,3,5]triazepin-2(7H)-thiones and N-alkyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-a][1,3,5]triazepin-2-amines. J. Comb Chem. 8:127-131, 2006.
  2. Houghten, R.A., Dooley, C.T., Appel, J.R. In vitro and direct in vivo testing of mixture-based combinatorial libraries for the identification of highly active and specific opiate ligands. The AAPS Journal 8:E371-382, 2006.
  3. Houghten, R.A., Dooley, C.T., Appel, J.R. Mixture-based combinatorial libraries. Handbook of Biologically Active Peptides, 1478-1494, 2006.
  4. Nefzi, A., Hoesl, C.E., Pinilla, C., Kauffman, G.B., Maggiora, G.M., Pasquale, E., Houghten, R.A. Synthesis of platinum(II) chiral tetraamine coordination complexes J. Comb. Chem. 8:780-783, 2006.
  5. Nefzi, A., Ostresh, J.M., Appel, J.R., Bidlack, J., Dooley, C.T., Houghten, R.A. Identification of potent and highly selective chiral tri-amine and tetra-amine u opoid receptors ligands. An example of lead optimization using mixture based libraries. Bioorg. Med. Chem. Lett. 16:4331-4338, 2006.

  6. Carter, B., Gronda, M., Wang, Z., Welsh, K., Pinilla, C., Andreeff, M., Schober, W., Nefzi, A., Pond, G., Mawji, I., Houghten, R., Ostresh, J., Brandwein, J., Minden, M., Schuh, A., Wells, R., Messner, H., Chun, K., Reed, J. Schimmer, A. Small-molecule XIAP inhibitors depress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells. Blood 105:4043-4050, 2005.
  7. Houghten, R.A. From Tens to Trillions - Advances in Synthetic Combinatorial Chemistry of Peptides, Peptidomimetics and Heterocyclic Compounds Derived from Peptides in press, Proceedings of the 19th APS. Understanding Biology Using Peptides, Blondelle, S. (Editor), 2005.
  8. Houghten, R.A., Yu, Y. "Volatilizable" supports for high-throughput organic synthesis. J. Am. Chem. Soc. 127:8582-8583, 2005.
  9. Kater, A.P., Dicker, F., Mangiola, M., Welsh, K., Houghten, R., Ostresh, J., Nefzi, A., Reed, J.C., Pinilla, C., Kipps, T.J. Inhibitors of XIAP sensitize CD40-activated chronic lymphocytic leukemia cells to CD95-mediated apoptosis. Blood 106:1742-1748, 2005.

  10. Hoesl, C.E., Nefzi, A., Houghten, R.A. Halogenoalkyl isocyanates a bifunctional reagents in an Aza-Wittig/heterocyclization reaction on the solid phase: efficient entry into new tetra-cyclic benzimidazole systems J. Comb. Chem. 6:220-223, 2004.
  11. Houghten, R.A., Dooley, C.T., Appel, J.R. De novo identification of highly active fluorescent kappa opioid ligands from a rhodamine labeled tetrapeptide positional scanning library. Bioorg. Med. Chem. Lett. 14:1947-1951, 2004.
  12. Nefzi, A., Ostresh, J.M., Yu, Y., Houghten, R.A. Combinatorial chemistry: libraries from libraries, the art of the diversity-oriented transformation of resin-bound peptides and chiral polyamides to low molecular weight acyclic and heterocyclic compounds. J. Org. Chem. 69:3603-3609, 2004.
  13. Orfi, L., Waczek, F., Pato, J., Varga, I., Hegymegi-Barakonyi, B., Houghten, R.A., Keri, G. Improved, high yield synthesis of 3H-quinazolin-4-ones, the key intermediates of recently developed drugs. Curr. Med. Chem. 11:2549-53, 2004
  14. Schimmer, A.D., Welsh, K., Pinilla, C., Wang, Z., Krajewska, M., Bonneau, M.-J., Pedersen, I.M., Kitada, S., Scott, F.L., Bailly-Maitre, B., Glinsky, G., Scudiero, D., Sausville, E., Salvesen, G., Nefzi, A., Ostresh, J.M., Houghten, R.A., Reed, J.C. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 5:25-35, 2004.
  15. Shukaliak, Quandt J., Borras, E., Prat, E., Gelderblom, H., Houghten, R.A., Kashani, A., Pinilla, C., Stuerzebecher, C.S., Martin, R. Peptidic complex mixtures as therapeutic agents in CNS autoimmunity. Mol. Immunol. 40:1075-1087, 2004.
  16. Wang, Z., Cuddy, M., Samuel, T., Welsh, K., Schimmer, A., Hanaii, F., Houghten, R., Pinilla, C., Reed, J.C. Cellular, biochemical, and genetic analysis of mechanism of small molecule IAP inhibitors. J. Biol. Chem. 279:48168-48176, 2004.
  17. Wilson, D.B., Wilson, D.H., Schroder, K., Pinilla, C., Blondelle, S., Houghten, R.A., Garcia, K.C. Specificity and degeneracy of T cells. Mol. Immunol. 40:1047-1055, 2004
  18. Yu, Y., Nefzi, A., Ostresh, J.M., Houghten, R.A. Parallel solid phase synthesis, mixture based combinatorial libraries & libraries from libraries: The versatility of chiral polyamines. In: Innovation and Perspectives in Solid Phase Synthesis & Combinatorial Libraries 2004 (Epton, R., Ed.), Mayflower Worldwide, Kingswinford, UK, pp. 1-4, 2004.
  19. Yu, Y., Ostresh, J.M., Houghten, R.A. A traceless approach for the solid-phase synthesis of 6-amino-1,3,5-triazine-2,4-diones. J. Comb. Chem. 6:83-85, 2004.
  20. Yu, Y., Ostresh, J.M., Houghten, R.A. Solid-phase synthesis of 5-aminotetrazoles. Tetrahedron Lett. 45:7787-7789, 2004.

  21. Hamashin, C., Spindler, L., Russell, S., Schink, A., Lambkin, I., O'Mahony, D., Houghten, R., Pinilla, C. Identification of novel small-molecule Ulex europaeus I mimetics for targeted drug delivery. Bioorg. Med. Chem. 11:4991-4997, 2003.
  22. Hoesl, C.E., Nefzi, A., Houghten, R.A. Parallel solid-phase synthesis of 2-imino-4-oxo-1,3,5-triazino[1,2-a]benzimidazoles via tandem aza-Wittig/heterocumulene-mediated annulation reaction. J. Comb. Chem. 5:155-160, 2003.
  23. Hoesl, C.E., Nefzi, A., Houghten, R.A. Abnormal aza-Wittig reaction on the solid phase: chemoselectivity studies towards the parallel synthesis of 3-aryl-2,4-dioxo-1,3,5-triazino[1,2-a]benzimidazoles Tetrahedron Lett. 44:3705-3708, 2003.
  24. Hoesl, C.E., Nefzi, A., Ostresh, J.M., Yu, Y., Houghten, R.A. Mixture-based combinatorial libraries: From peptides and peptidomimetics to small molecule acyclic and heterocyclic compounds. Methods Enzymol. 369:496-517, 2003.
  25. Lambkin, I., Pinilla, C., Hamashin, C., Spindler, L., Russell, S., Schink, A., Moya-Castro, R., Allicotti, G., Higgins, L., Smith, M., Dee, J., Wilson, C., Houghten, R., O'Mahony, D. Toward targeted oral vaccine delivery systems: selection of lectin mimetics from combinatorial libraries. Pharm. Res. 20:1258-1266, 2003.
  26. Nefzi, A., Ostresh, J.M., Houghten, R.A. Combinatorial chemistry: Mixture-based combinatorial libraries of acyclic and heterocyclic compounds from amino acids and short peptides. In: Modern Methods of Drug Discovery (Hillisch, A., Hilgenfeld, R., Eds.) Birkhäuser Verlag, Basel, pp. 109-123, 2003.
  27. Nefzi, A., Vidal, A., Rinnova, M., Houghten, R.A. N-Substituted benzotriazole: Useful template for the solid-phase synthesis of diverse small molecule compounds. In: Innovation and Perspectives in Solid Phase Synthesis & Combinatorial Libraries 2002 (Epton, R., Ed.), Mayflower Worldwide, Kingswinford, UK, pp. 185-188, 2003.
  28. Pinilla, C., Appel, J.R., Borras, E., Houghten, R.A. Advances in the use of synthetic combinatorial chemistry: Mixture-based libraries. Nat. Med. 9:118-122, 2003.
  29. Yu, Y., Ostresh, J.M., Houghten, R.A. The combined solid/solution-phase synthesis of nitrosamines: the evolution of the "libraries from libraries" concept. J. Org. Chem. 68:183-186, 2003.
  30. Yu, Y., Ostresh, J.M., Houghten, R.A. Solid-phase synthesis of indolines via palladium-catalyzed cyclization. Tetrahedron Lett. 44:2569-2572, 2003.
  31. Yu, Y., Ostresh, J.M., Houghten, R.A. Solid-phase synthesis of 3-amino-1,2,4-triazoles. Tetrahedron Lett. 44:7841-7843, 2003.

  32. Acharya, A.N., Ostresh, J.M., Houghten, R.A. Solid-phase parallel synthesis of dihydroimidazolyl dihydrobenzimidazol-2-ones. Tetrahedron 58:2095-2100, 2002.
  33. Acharya, A.N., Ostresh, J.M., Houghten, R.A. Solid-phase parallel synthesis of substituted dihydroimidazolyl dihydroimidazol-3-ium salts. Tetrahedron Lett. 43:1157-1160, 2002.
  34. Acharya, A.N., Ostresh, J.M., Houghten, R.A. Solid-phase parallel synthesis of dihydroimidazolyl dihydroquinoxalin-2(1H)-ones. Tetrahedron 58:221-225, 2002.
  35. Acharya, A.N., Ostresh, J.M., Houghten, R.A. Determination of isokinetic ratios necessary for equimolar incorporation of carboxylic acids in the solid-phase synthesis of mixture-based combinatorial libraries. Biopolymers 65:32-39, 2002.
  36. Acharya, A.N., Ostresh, J.M., Houghten, R.A. Novel approaches for the solid-phase synthesis of biheterocyclic dihydroimidazole analogues. J. Comb. Chem. 4:214-222, 2002.
  37. Acharya, A.N., Thai, C., Ostresh, J.M., Houghten, R.A. Use of Vilsmeier reagent for the solid-phase synthesis of 1,5-disubstituted 4,5-dihydro-1H-imidazoles and disubstituted 4,5-dihydro-1H-imidazolyl benzimidazoles. J. Comb. Chem. 4:496-500, 2002.
  38. Borras, E., Martin, R., Judkowski, V., Shukaliak, J., Zhao, Y., Rubio-Godoy, V., Valmori, D., Wilson, D., Simon, R., Houghten, R., Pinilla, C. Findings on T cell specificity revealed by synthetic combinatorial libraries. J. Immunol. Methods 267:79-97, 2002.
  39. Dutoit, V., Rubio-Godoy, V., Pittet, M.J., Zippelius, A., Dietrich, P.Y., Legal, F.A., Guillaume, P., Romero, P., Cerottini, J.C., Houghten, R.A., Pinilla, C., Valmori, D. Degeneracy of antigen recognition as the molecular basis for the high frequency of naive A2/Melan-a peptide multimer+ CD8+ T cells in humans. J. Exp. Med. 196:207-216, 2002.
  40. Klein, G., Acharya, A.N., Ostresh, J.M., Houghten, R.A. Parallel solid-phase synthesis of trisubstituted triazinobenzimidazolediones. J. Comb. Chem. 4:345-351, 2002.
  41. Nefzi, A., Giulianotti, M., Truong, L., Rattan, S., Ostresh, J.M., Houghten, R.A. Solid phase synthesis of linear ureas tethered to hydantoins and thiohydantoins. J. Comb. Chem. 4:175-178, 2002.
  42. Nefzi, A., Mimna, R.A., Houghten, R.A. Parallel solid-phase synthesis of 1,6-piperazine-2-ones J. Comb. Chem. 4:542-545, 2002.
  43. Pinilla, C., Giulianotti, M., Houghten, R. How to screen trillions of drug candidate compounds SP2 June:36-37, 2002.
  44. Pinilla, C., Giulianotti, M., Houghten, R. Mixed libraries speed up HTS even further SP2 August:18-19, 2002.
  45. Rinnova, M., Nefzi, A., Houghten, R.A. An expedient method for solid-phase synthesis of α-aminoalkyl phosphopeptides. Tetrahedron Lett. 43:4103-4106, 2002
  46. Rinnova, M., Nefzi, A., Houghten, R.A. An efficient approach for solid-phase synthesis of peptidomimetics based on 4-imidazolidinones. Tetrahedron Lett. 43:2343-2346, 2002.
  47. Rinnova, M., Nefzi, A., Houghten, R.A. Opioid activity of 4-imidazolidinone positional analogues of Leu-Enkephalin Bioorg. Med. Chem. Lett. 12: 3175-3178, 2002.
  48. Rinnova, M., Vidal, A., Nefzi, A., Houghten, R.A. Solid-phase synthesis of 1,2,5-trisubstituted 4-imidazolidinones. J. Comb. Chem. 4:209-213, 2002.
  49. Rubio-Godoy, V., Ayyoub, M., Dutoit, V., Servis, C., Schink, A., Rimoldi, D., Romero, P., Cerottini, J.-C., Simon, R., Zhao, Y., Houghten, R.A., Pinilla, C., Valmori, D. Combinatorial peptide library based identification of peptide ligands for tumor-reactive cytolytic T lymphocytes of unknown specificity. Eur. J. Immunol. 32: 2292-2299, 2002.
  50. Rubio-Godoy, V., Dutoit, V., Zhao, Y., Simon, R., Guillaume, P., Houghten, R.A., Romero, P., Cerottini, J.C., Pinilla, C., Valmori, D. Positional scanning-synthetic peptide library-based analysis of self- and pathogen-derived peptide coss-reactivity with tumor-reactive Melan-A-specific CTL. J. Immunol. 169:5696-5707, 2002.
  51. Rubio-Godoy, V., Pinilla, C., Dutoit, V., Borras, E., Simon, R., Zhao, Y., Cerottini, J.-C., Romero, P., Houghten, R.A., Valmori, D. Toward synthetic combinatorial peptide libraries in positional scanning format PS-SCL based identification of CD8+ tumor reactive T cell ligands: a comparative analysis of PS-SCL recognition by a single tumor-reactive CD8+ CTL clone. Cancer Research, 62:2058-2063, 2002.
  52. Yu, Y., Ostresh, J.M., Houghten, R.A. Solid phase synthesis of 1,5-disubstituted-2-aryliminoimidazolidines. J. Org. Chem. 67:3138-3141, 2002.
  53. Yu, Y., Ostresh, J.M., Houghten, R.A. Solid-phase parallel synthesis of 2-aminoimidazolidin-4-ones. Tetrahedron 58:3349-3353, 2002.
  54. Yu, Y., Ostresh, J.M., Houghten, R.A. Efficient solid-phase synthesis of 1,3,5-trisubstituted-1,3,5-triazine-2,4,6-trione derivatives. J. Comb. Chem. 4:484-490, 2002.
  55. Yu, Y., Ostresh, J.M., Houghten, R.A. A traceless approach for the parallel solid-phase synthesis of 2-(arylamino)quinazolinones. J. Org. Chem. 67:5831-5834, 2002.

  56. Acharya, A.N., Nefzi, A., Ostresh, J.M., Houghten, R.A. Tethered libraries: Solid-phase synthesis of substituted urea-linked bicyclic guanidines. J. Comb. Chem. 3:189-195, 2001.
  57. Acharya, A.N., Ostresh, J.M., Houghten, R.A. A novel approach for the solid-phase synthesis of substituted imidazolines and bis-imidazolines. J. Org. Chem. 66:8673-8676, 2001.
  58. Acharya, A.N., Ostresh, J.M., Houghten, R.A. A novel approach for the solid-phase synthesis of substituted cyclic guanidines, their respective bis analogs, and N-acylated guanidines from N-acylated amino acid amides. J. Comb. Chem. 3:578-589, 2001.
  59. Acharya, A.N., Ostresh, J.M., Houghten, R.A. Solid-phase synthesis of bis-cyclic guanidines from tripeptides. Tetrahedron 57:9911-9914, 2001.
  60. Acharya, A.N., Ostresh, J.M., Houghten, R.A. Solid-phase synthesis of substituted imidazoline-tethered 2,3-diketopiperazines, cyclic ureas, and cyclic thioureas. J. Comb. Chem. 3:612-623, 2001.
  61. Acharya, A.N., Ostresh, J.M., Nefzi, A., Houghten, R.A. Solid-phase synthesis of substituted dihydroimidazoles and their bis analogs. In: Peptides: The Wave of the Future: Proceedings of the 2nd International/17th American Peptide Symposiium (Lebl, M. and Houghten, R.A., Eds.), Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 255-256, 2001.
  62. Bokonyi, G., Horvath, A., Orfi, L., Szabo, E.Z., Houghten, R.A., Ostresh, J.M., Idei, M., Hollosy, F., Szende, B., Teplan, I., Keri, G. Screening of peptidomimetic libraries for antitumor activity. In: Peptides 2000: Proceedings of the Twenty-Sixth European Peptide Symposium (Martinez, J. and Fehrentz, J.-A., Eds.), EDK, Paris, pp. 791-792, 2001.
  63. Dooley, C.T., Mabini, A., Sylvester, T., Appel, J.R., Houghten, R.A. Identification of novel ligands for vasopressin V2 receptor from positional scanning libraries. In: Peptides: The Wave of the Future. Proceedings of the 2nd International/17th American Peptide Symposium. (Houghten, R.A., Lebl, M., Eds.), Kluwer Academic Publishers, Dordrecht, pp. 921-922, 2001.
  64. Eichler, J., Houghten, R.A. Combinatorial synthesis. In: Methods of Organic Chemistry, Synthesis of Peptides and Peptidomimetics. (Goodman, M., Editor-in-Chief), Vol. E22a, p.844-866. Thieme Stuttgart, New York, 2001.
  65. La Rosa, C., Krishnan, R., Markel, S., Schneck, J.P., Houghten, R.A., Pinilla, C., Diamond, D.J. Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from positional scanning synthetic combinatorial libraries. Blood 97:1776-1786, 2001.
  66. Nefzi, A., Giulianotti, M.A., Houghten, R.A. Solid-phase synthesis of bis-heterocyclic compounds from resin-bound orthogonally protected lysine. J. Comb. Chem. 3:68-70, 2001.
  67. Nefzi, A., Giulianotti, M.A., Ong, N.A., Ostresh, J.M., Dooley, C.T., Blondelle, S.E., Houghten, R.A. Solid phase synthesis of acyclic and heterocyclic combinatorial libraries from resin-bound triamines. In: Innovation and Perspectives in Solid Phase Synthesis & Combinatorial Libraries 2000 (Epton, R., Ed.), Mayflower Worldwide, Birmingham, UK, pp. 119-122, 2001.
  68. Nefzi, A., Houghten, R.A. Polyamines as intermediates for the synthesis of heterocyclic compounds and oligomeric heterocyclic compounds from resin-bound polyamides. In: Peptides: The Wave of the Future. Proceedings of the 2nd International/17th American Peptide Symposium. (Houghten, R.A., Lebl, M., Eds.), Kluwer Academic Publishers, Dordrecht, pp. 252-254, 2001.
  69. Nefzi, A., Ong, N.A, Houghten, R.A. Parallel synthesis of 4,5-dihydro-1H-1,4-benzodiazepine-2,3-diones. Tetrahedron Lett. 42:5141-5143, 2001.
  70. Nefzi, A., Ostresh, J.M., Houghten, R.A. Solid phase synthesis of mixture-based acyclic and heterocyclic small molecule combinatorial libraries from resin-bound polyamides. Biopolymers (Peptide Science) 60:212-219, 2001.
  71. Orfi, L., Bokonyi, G., Horvath, A., Houghten, R.A., Ostresh, J.M., Teplan, I., Keri, G. New antiproliferative agents from a peptidomimetic library. In: Peptides: The Wave of the Future: Proceedings of the 2nd International/17th American Peptide Symposiium (Lebl, M. and Houghten, R.A., Eds.), Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 640-641, 2001.
  72. Pinilla, C., Appel, J.R., Houghten, R.A. Identification of B cell and T cell epitopes using synthetic peptide combinatorial libraries. In: Current Protocols in Immunology (J.E. Coligan, A.M. Krusibeek, D.H. Margulies, E.M. Shevach, and W. Strober, Eds.) John Wiley & Sons, Inc., New York. pp. 9.5.1-9.5.13, 2001.
  73. Pinilla, C., Rubio-Godoy, V., Dutoit, V., Guillaume, P., Simon, R., Zhao, Y., Houghten, R., Cerottini, J., Romero, P., Valmori, D. Combinatorial peptide libraries as an alternative approach to the identification of ligands for tumor reactive cytolytic T. lymphocytes. Cancer Research, 61:5153-5160, 2001.
  74. Rinnova, M., Vidal, A., Nefzi, A., Houghten, R.A. Solid phase synthesis of 1,2,5-substituted derivatives of 4-imidazolidinone. In: Peptides: The Wave of the Future. Proceedings of the 2nd International/17th American Peptide Symposium. (Houghten, R.A., Lebl, M., Eds.), Kluwer Academic Publishers, Dordrecht, pp. 257-258, 2001.
  75. Tai, K.-K., Blondelle, S.E., Ostresh, J.M., Houghten, R.A., Montal, M. An N-methyl-D-aspartate receptor channel blocker with neuroprotective activity. Proc. Natl. Acad. Sci. USA 98:3519-3524, 2001.
  76. Vidal, A., Nefzi, A., Houghten, R.A. Solid-phase synthesis of α,α-difluoro-β-amino acids via the Reformatsky reaction. J. Org. Chem. 66:8268-8272, 2001.
  77. Vidal, A., Nefzi, A., Houghten, R.A. Solid-phase synthesis of α-difluoro-β-amino acids by a Reformatsky reaction. In: Peptides: The Wave of the Future. Proceedings of the 2nd International/17th American Peptide Symposium. (Houghten, R.A., Lebl, M., Eds.), Kluwer Academic Publishers, Dordrecht, pp. 261-262, 2001.
  78. Winiewski, K., Suciras-Diaz, J., Schteingart, C., Galyean, R., Houghten, R., Vanderah, T., Porreca, F., Riviere, P., Junien, J.L., Trojnar, J. Long acting, selective, peripheral, kappa agonists. In: Peptides 2000: Proceedings of the Twenty-Sixth European Peptide Symposium (Martinez, J. and Fehrentz, J.-A., Eds.), EDK, Paris, pp. 775-776, 2001.
  79. Yu, Y., El Abdellaoui, H.M., Ostresh, J.M., Houghten, R.A. Solid-phase synthesis of [3,5,7]-1H-imidazo[1,5-a]imidazol-2(3H)-ones. Tetrahedron Lett. 42:623-625, 2001.
  80. Yu, Y., Ostresh, J.M., Houghten, R.A. Solid phase synthesis of 1,2,4-triazinan-3-ones. In: Peptides: The Wave of the Future: Proceedings of the 2nd International/17th American Peptide Symposiium (Lebl, M. and Houghten, R.A., Eds.), Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 259-260, 2001.
  81. Yu, Y., Ostresh, J.M., Houghten, R.A. Solid phase synthesis of 2,3,5-trisubstituted-4H-imidazolones. J. Comb. Chem. 3:521-523, 2001.
  82. Yu, Y., Ostresh, J.M., Houghten, R.A. Solid-phase synthesis of 1,7-disubstituted 1,3,4-triazepane-2,4-diones. Org. Letters 3:2797-2799, 2001.

  83. Alvarez-Gutierrez, J.M., Nefzi, A., Houghten, R.A. Solid phase synthesis of 1,3-disubstituted succinimides. Tetrahedron Lett. 41:609-612, 2000.
  84. Alvarez-Gutierrez, J.M., Nefzi, A., Houghten, R.A. Solid phase synthesis of 1-substituted pyroglutamates. Tetrahedron Lett. 41:851-854, 2000.
  85. Cameron, A., Appel, J., Houghten, R.A., Lindberg, I. Polyarginines are potent furin inhibitors. J. Biol. Chem. 275:36741-36749, 2001.
  86. Dooley, C.T., Houghten, R.A. New opioid peptides, peptidomimetic, and heterocyclic compounds from combinatorial libraries. Biopolymers (Peptide Science) 51:379-390, 2000.
  87. Dooley, C.T., Houghten, R.A. Orphanin FQ/Nociceptin receptor binding studies. Peptides 21:949-960, 2000.
  88. Dörner, B., Ostresh, J.M., Houghten, R.A., Frank, R., Tiepold, A., Fox, J.E., Bray, A.M., Ede, N.J., James, I.W., Wickham, G. Manual multiple synthesis methods, 1. Simultaneous multiple peptide synthesis - the T-bag method. In: Fmoc Solid Phase Peptide Synthesis - A Practical Approach (Chan, W.C. and White, P.D., Eds.), Oxford University Press, Oxford, pp. 303-327, 2000.
  89. Hemmer, B., Kondo, T., Gran, B., Pinilla, C., Cortese, I., Pascal, J., Tzou, A., McFarland, H.F., Houghten, R.A., Martin, R. Minimal peptide length requirements for CD4 T cell clones-implications for molecular mimicry and T cell survival. Int. Immunol. 12:375-383, 2000.
  90. Hemmer, B., Pinilla, C., Gran, B., Vergelli, M., Ling, N., Conlon, P., McFarland, H.F., Houghten, R.A., Martin, R. Contribution of individual amino acids within MHC molecule or antigenic peptide to TCR ligand potency. J. Immunol. 164:861-871, 2000.
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  190. Mor, G., Yamshchikov, G., Sedegah, M., Takeno, M., Wang, R., Houghten, R.A., Hoffman, S., Kilnman, D.M. Induction of neonatal tolerance by plasmid DNA vaccination of mice. J. Clin. Invest. 98:2700-2705, 1996.
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  192. Pender, M.P., Csurhes, P.A., Houghten, R.A., McCombe, P.A., Good, M.F. A study of human T-cell lines generated from multiple sclerosis patients and controls by stimulation with peptides of myelin basic protein. J. Neuroimmunol. 70:65-74, 1996.
  193. Pérez-Payá, E., Forood, B., Houghten, R.A., Blondelle, S.E. The structural characterization and 5'-mononucleotide binding of polyalanine β-sheet complexes. J. Mol. Recogn. 9:488-493, 1996.
  194. Pérez-Payá, E., Houghten, R.A., Blondelle, S.E. Functionalized protein-like structures from conformationally defined synthetic combinatorial libraries. J. Biol. Chem. 271:4120-4126, 1996.
  195. Pérez-Payá, E., Houghten, R.A., Blondelle, S.E. The design of self-assembling peptide complexes using conformationally defined libraries. In: Techniques in Protein Chemistry VII. (D.R. Marshak, Ed.) Academic Press, San Diego, pp. 65-71, 1996.
  196. Pérez-Payá, E., Takahashi, E., Mingarro, I., Houghten, R.A., Blondelle, S.E. Use of synthetic combinatorial libraries to identify peptide inhibitors of Ca2+-complexed calmodulin. In: Peptides: Chemistry, Structure and Biology. Proceedings of the Fourteenth American Peptide Symposium (PTP Kaumaya, RS Hodges, Eds) Mayflower Scientific Ltd, Kingswinford, UK, pp. 303-304, 1996.
  197. Pinilla, C., Appel, J.R., Houghten, R.A. Tea bag synthesis of positional scanning synthetic combinatorial libraries and their use for mapping antigenic determinants. In: Methods In Molecular Biology: Epitope MappIn:g Protocols (Morris, G. E., Eds.), Humana Press In:c., Totowa, NJ, pp. 171-179, 1996.
  198. Pinilla, C., Appel, J.R., Blondelle, S.E., Dooley, C.T., Dörner, B., Eichler, J., Ostresh, J.M., Houghten, R.A. Synthetic combinatorial libraries screened in solution. In: Peptides: Chemistry, Structure and Biology, Proceedings of the Fourteenth American Peptide Symposium (Kaumaya, P.T.P. and Hodges, R.S., Eds.), Mayflower Scientific, Ltd., Kingswinford, UK, pp. 884-886, 1996.
  199. Pinilla, C., Appel, J.R., Dooley, C.T., Blondelle, S.E., Eichler, J., Dörner, B., Ostresh, J.M., Houghten, R.A. The versatility of nonsupport-bound combinatorial libraries. In: Combinatorial Peptide and Nonpeptide Libraries (Jung, G., Ed.), Verlag Chemie, Wienheim, pp. 139-171, 1996.

  200. Appel, J.R., Buencamino, J., Houghten, R.A., Pinilla, C. Study of peptide-antibody interactions using a decapeptide positional scanning library. In: Peptides 94: Proceedings of the 23rd European Peptide Symposium (Maia, H. L. S., Eds.), ESCOM, Leiden, pp. 815-816, 1995.
  201. Blondelle, S.E., Ostresh, J.M., Houghten, R.A., Pérez-Payá, E. Induced conformational states of amphipathic peptides in aqueous/lipid environments. Biophys. J. 68:351-359, 1995.
  202. Blondelle, S.E., Pérez-Payá, E., Allicotti, G., Forood, B., Houghten, R.A. Peptide binding domains determined through chemical modification of the side-chain functional groups. Biophys. J. 69:604-611, 1995.
  203. Blondelle, S.E., Pérez-Payá, E., Dooley, C.T., Pinilla, C., Houghten, R.A. Soluble combinatorial libraries of organic, peptidomimetic and peptide diversities. Trends Anal. Chem. 14:83-92, 1995.
  204. Blondelle, S.E., Takahashi, E., Dinh, K.T., Houghten, R.A. The antimicrobial activity of hexapeptides derived from synthetic combinatorial libraries. J. Appl. Bacteriol. 78:39-46, 1995.
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  206. Cuervo, J.H., Weitl, F., Ostresh, J.M., Hamashin, V.T., Hannah, A.L., Houghten, R.A. Polyalkylamine chemical combinatorial libraries. In: Peptides 94: Proceedings of the 23rd European Peptide Symposium (Maia, H.L.S., Ed.), ESCOM, Leiden, pp. 465-466, 1995.
  207. Dooley, C.T., Hope, S.K., Houghten, R.A. Identification of tetrameric opioid peptides from a combinatorial library composed of L-, D- and non-proteinogenic amino acids. In: Peptides 94: Proceedings of the 23rd European Peptide Symposium (Maia, H. L. S., Eds.), ESCOM, Leiden, pp. 805-806, 1995.
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  209. Dooley, C.T., Houghten, R.A. Identification of mu-selective polyamine antagonists from a synthetic combinatorial library. Analgesia 1:400-404, 1995.
  210. Dooley, C.T., Kaplan, R.A., Chung, N.N., Schiller, P.W., Bidlack, J.M., Houghten, R.A. Six highly active mu-selective opioid peptides identified from two synthetic combinatorial libraries. Pept. Res. 8:124-137, 1995.
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  218. Malik, A., Houghten, R., Corradin, G., Buus, S., Berzofsky, J., Hoffman, S.L. Identification of a nonameric H-2Kk-restricted CD8+ cytotoxic T lymphocyte epitope on the Plasmodium falciparum circumsporozoite protein. Infection and Immunity 63:1955-1959, 1995.
  219. Marcos, J.F., Beachy, R.N., Houghten, R.A., Blondelle, S.E., Pérez-Payá, E. Inhibition of a plant virus infection by analogs of melittin. Proc. Natl. Acad. Sci. USA 92:12466-12469, 1995.
  220. Mingarro, I., Pérez-Payá, E., Pinilla, C., Appel, J.R., Houghten, R.A., Blondelle, S.E. Activation of bee venom phospholipase A2 through a peptide-enzyme complex. FEBS Letters 372:131-134, 1995.
  221. Ostresh, J.M., Hamashin, V.T., Husar, G.M., Dörner, B., Houghten, R.A. Direct determination of the extent of racemization during post peptide synthesis reactions. In: Peptides 94: Proceedings of the 23rd European Peptide Symposium (Maia, H.L.S., Ed.), ESCOM, Leiden, pp. 416-417, 1995.
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  225. Pinilla, C., Buencamino, J., Appel, J.R., Hopp, T.P., Houghten, R.A. Mapping the detailed specificity of a calcium-dependent monoclonal antibody through the use of soluble positional scanning combinatorial libraries: Identification of potent calcium-independent antigens. Mol. Div. 1:21-28, 1995.
  226. Pinilla, C., Buencamino, J., Appel, J.R., Houghten, R.A., Brassard, J.A., Ruggeri, Z.M. Two antipeptide monoclonal antibodies that recognize adhesive sequences in fibrinogen: Identification of antigenic determinants and unrelated sequences using synthetic combinatorial libraries. Biomedical Peptides, Proteins & Nucleic Acids 1:199-204, 1995.
  227. Pinilla, C., Buencamino, J., Houghten, R.A., Appel, J.R. Detailed studies of antibody specificity using synthetic peptide combinatorial libraries. In: Vaccines 1995: Molecular Approaches to the Control of Infectious Diseases (Brown, F., Chanock, R. M., Ginsberg, H. S., and Norrby, E., Eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp. 1-6, 1995.
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  229. Pinilla, C., Chendra, S., Appel, J.R., Houghten, R.A. Elucidation of monoclonal antibody polyspecificity using synthetic combinatorial library. Peptide Res. 8:250-257, 1995.
  230. Puras Lutzke, R.A., Eppens, N.A., Weber, P.A., Houghten, R.A., Plasterk, R.H.A. Identification of a hexapeptide inhibitor of the human immunodeficiency virus integrase protein by using a combinatorial chemical library. Proc. Natl. Acad. Sci. 92:11456-11460, 1995.
  231. Quakyi, I.A., Miller, L.H., Good, M.F., Ahlers, J.D., Isaacs, S.N., Nunberg, J.H., Houghten, R.A., Keister, D.B., Coligan, J.E., Moss, B., Alling, D., Berzofsky, J.A., Kaslow, D.C. Synthetic peptides from P. falciparum sexual stage 25-kDa protein induce antibodies that react with the native protein: the role of IL-2 and conformational structure on immunogenicity of Pfs25. Pept. Res. 8:335-344, 1995.
  232. Wizel, B., Houghten, R., Church, P., Tine, J.A., Lanar, D.E., Gordon, D.M., Ballou, W.R., Sette, A., Hoffman, S.L. HLA-A2-Restricted cytotoxic T lymphocyte responses to multiple Plasmodium falciparum sporozoite surface protein 2 epitopes in sporozoite-immunized volunteers. J. Immunol. 155:766-775, 1995.
  233. Wizel, B., Houghten, R.A., Parker, K.C., Coligan, J.E., Church, P., Gordon, D.M., Ballou, W.R., Hoffman, S.L. Irradiated sporozoite vaccine induces HLA-B8-restricted cytotoxic T lymphocyte responses against two overlapping epitopes of the Plasmodium falciparum sporozoite surface protein 2. J. Exp. Med. 182:1435-1445, 1995.

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  235. Blondelle, S.E., Simpkins, L.R., Houghten, R.A. Inhibitors of cytolytic compounds identified using synthetic peptide libraries. In: Innovation and Perspectives in Solid Phase Synthesis. Peptides, Proteins and Nucleic Acids (R Epton, Ed.) Mayflower Worldwide Limited, Birmingham, pp. 163-168, 1994.
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  237. Churchill, M.E.A., Stura, E., Pinilla, C., Appel, J.R., Houghten, R.A., Kono, D.H., Balderas, R.S., Fieser, G.G., Schulze-Gahmen, U., Wilson, I.A. Crystal structure of a peptide complex of anti-influenza peptide antibody Fab 26/9: Comparison of two different antibodies bound to the same peptide antigen. J. Mol. Biol. 241:534-556, 1994.
  238. Dooley, C.T., Chung, N.N., Wilkes, B.C., Schiller, P.W., Bidlack, J.M., Pasternak, G.W., Houghten, R.A. An all D-amino acid opioid peptide with central analgesic activity from a combinatorial library. Science 266:2019-2022, 1994.
  239. Dooley, C.T., Hope, S., Houghten, R.A. Rapid identification of novel opioid peptides from an N-acetylated synthetic combinatorial library. Regul. Pept. 54:87-88, 1994.
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  242. Eichler, J., Pinilla, C., Chendra, S., Appel, J.R., Houghten, R.A. Synthesis of peptide libraries on cotton carriers: methods and applications. In: Innovation and Perspectives in Solid Phase Synthesis - Peptides, Proteins and Nucleic Acids (Epton, R., Ed.), Mayflower Worldwide Limited, Birmingham, pp. 227-232, 1994.
  243. Flippen-Anderson, J.L., Deschamps, J.R., Ward, K.B., George, C., Houghten, R. Crystal structure of a deltakephalin: a δ-selective opioid peptide with a novel β bend-like conformation. Int. J. Pept. Prot. Res. 44:97-104, 1994.
  244. Houghten, R.A. Combinatorial libraries: Finding the needle in the haystack. Current Biology 4:564-567, 1994.
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  248. Jezek, J., Houghten, R.A. A comparative study of BOP as a coupling agent using simultaneous multiple peptide synthesis. Collect.Czech.Chem.Commun. 59:691-706, 1994.
  249. Muro, Y., Tsai, W.-M., Houghten, R., Tan, E.M. Synthetic combinatorial peptide simulating antigenicity of conformation-dependent autoepitope. J. Biol. Chem. 269:18529-18534, 1994.
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  252. Pérez-Payá, E., Houghten, R.A., Blondelle, S.E. Determination of the secondary structure of selected melittin analogues with different haemolytic activities. Biochem. J. 299:587-591, 1994.
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  255. Pinilla, C., Appel, J.R., Houghten, R.A. Investigation of antigen-antibody interactions using a soluble nonsupport-bound synthetic decapeptide library composed of four trillion sequences. Biochem. J. 301:847-853, 1994.
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  257. Pinilla, C., Appel, J.R., Milich, D., Houghten, R.A. Identification of an antigenic determinant for the surface antigen of hepatitis B virus using peptide libraries. In: Peptides: Chemistry, Structure and Biology, Proceedings of the 13th American Peptide Symposium (Hodges, R. S. and Smith, J. A., Eds.), ESCOM, Leiden, pp. 1016-1017, 1994.
  258. Pokorny, V., Mudra, P., Jehnicka, J., Zenisek, K., Pavlik, M., Voburka, Z., Rinnova, M., Stierandova, A., Lucka, A.W., Eichler, J., Houghten, R., Lebl, M. COMPAS 242. New type of multiple peptide synthesizer utilizing cotton and tea bag technology. In: Innovation and Perspectives in Solid Phase Synthesis: Peptides, Proteins and Nucleic Acids (Epton, R., Ed.) Mayflower Worldwide Limited, Birmingham, pp. 643-648, 1994.
  259. Quakyi, I.A., Currier, J., Fell, A., Taylor, D.W., Roberts, T., Houghten, R.A., England, R.D., Berzofsky, J.A., Miller, L.H., Good, M.F. Analysis of human T cell clones specific for conserved peptide sequences within malaria proteins. Paucity of clones responsive to intact parasites. J. Immunol. 153: 2082-2092, 1994.
  260. Shirai, M., Okada, H., Nishioka, M., Akatsuka, T., Wychowski, C., Houghten, R., Feinstone, S., Berzofsky, J.A. An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans. J. Virol. 68:3334-3342, 1994.
  261. Weber, P., Blanc, P., Bloyer, R., Houghten, R.A. Potent anti-herpes simplex virus type 1 activity of peptides identified through the use of a synthetic peptide combinatorial library. In: Recent Advances in Chemotherapy (J. Einhorn, C.R. Nord & S. R. Norrby, Eds.) American Society for Microbiology, Washington, D.C. pp. 649-650, 1994.
  262. Wizel, B., Rogers, W.O., Houghten, R.A., Lanar, D.E., Tine, J.A., Hoffman, S.L. Induction of murine cytotoxic T lymphocytes against Plasmodium falciparum sporozoite surface protein 2. Eur. J. Immunol. 24:1487-1495, 1994.

  263. Blondelle, S.E., Houghten, R.A. Comparison of 55% TFA/CH2Cl2 and 100% TFA for Boc group removal during solid-phase peptide synthesis. Int. J. Pept. Protein Res. 41:522-527, 1993.
  264. Blondelle, S.E., Simpkins, L.R., Houghten, R.A. Inhibition of melittin's hemolytic activity using synthetic peptide combinatorial libraries. In: Peptides 1992: Proceedings of the 22nd European Peptide Symposium (Schneider, C.H., Eberle, A.N., Eds.) ESCOM Science Publishers B.V. Leiden, pp. 761-762, 1993.
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  266. Boehncke, W.-H., Takeshita, T., Pendleton, C.D., Houghten, R.A., Sadegh-Nasseri, S., Racioppi, L., Berzofsky, J.A., Germain, R.N. The importance of dominant negative effects of amino acid side chain substitution in peptide-MHC molecule interactions and T cell recognition. J. Immunol. 150:331-341, 1993.
  267. Doolan, D.L., Khamboonruang, C., Beck, H.-P., Houghten, R.A., Good, M.F. Cytotoxic T lymphocyte (CTL) low-responsiveness to the Plasmodium falciparum circumsporozoite protein in naturally-exposed endemic populations: anaylsis of human CTL response to most know variants. Int. Immunol. 5:37-46, 1993.
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  271. Eichler, J., Houghten, R.A. Identification of substrate-analog trypsin inhibitors through the screening of synthetic peptide combinatorial libraries. Biochemistry 32:11035-11041, 1993.
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  282. Pinilla, C., Appel, J.R., Chendra, S., Houghten, R.A. Determination of multiple binding specificities of a monoclonal antibody using a synthetic peptide combinatorial library. In: Peptides 1992: Proceedings of the 22nd European Peptide Symposium (Schneider, C. H. and Eberle, A. N., Eds.), ESCOM Science Publishers B.V., Leiden, pp. 903-904, 1993.
  283. Roos, G., Landberg, G., Huff, J.P., Houghten, R., Takasaki, Y., Tan, E.M. Analysis of the epitopes of proliferating cell nuclear antigen recognized by monoclonal antibodies. Lab. Investig. 68:204-210, 1993.

  284. Appel, J.R., Pinilla, C., Houghten, R.A. Identification of related peptides recognized by a monoclonal antibody using a synthetic peptide combinatorial library. Immunomethods 1:17-23, 1992.
  285. Barnes, P.F., Mehra, V., Rivoire, B., Fong, S.-J., Brennan, P.J., Voegtline, M.S., Minden, P., Houghten, R.A., Bloom, B.R., Modlin, R.L. Immunoreactivity of a 10-kDa antigen of Mycobacterium tuberculosis. J. Immunol. 148:1835-1840, 1992.
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  288. Blondelle, S.E., Houghten, R.A. Design of model peptides having potent antimicrobial activities. Biochemistry 31:12688-12694, 1992.
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  297. Houghten, R.A., Blondelle, S.E., Cuervo, J.H. Development of new antimicrobial agents using a synthetic peptide combinatorial library involving more than 34 million hexamers. In: Innovation and Perspectives in Solid Phase Synthesis: Peptides, Polypeptides and Oligonucleotides (R Epton, Ed.) Intercept Ltd, Andover, UK, pp. 237-239, 1992.
  298. Houghten, R.A., Cuervo, J.H., Pinilla, C., Appel, J.R., Dooley, C.T., Blondelle, S.E. The use of a peptide library composed of 34 012 224 hexamers for basic research and drug discovery. In: Peptides, Proceedings of the Twelfth American Peptide Symposium (JA Smith and JE Rivier, Eds.) ESCOM Science Publishers B.V. Leiden, pp. 560-561, 1992.
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  300. Pinilla, C., Appel, J.R., Blanc, P., Houghten, R.A. Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries. Biotechniques 13:901-905, 1992.
  301. Pinilla, C., Appel, J.R., McPherson, S.E., Houghten, R.A. Comparison of structural and functional approaches for the study of peptide-mAb interactions. In: Peptides. Proceedings of the Twelfth American Peptide Symposium (Smith, J. A. and Rivier, J. E., Eds.), ESCOM Science Publishers B.V., Leiden, pp. 867-868, 1992.
  302. Pride, M.W., Thanavala, Y.M., Strick, N., Houghten, R.A., Neurath, A.R. Toleration of amino acid substitutions within hepatitis B virus envelope protein epitopes established by peptide replacement set analysis. II. region S(122-136). Peptide Res. 5(4):217-226, 1992.
  303. Pruksakorn, S., Galbraith, A., Houghten, R.A., Good, M.F. Conserved T and B cell epitopes on the M protein of Group A streptococci - induction of bactericidal antibodies. J. Immunol. 149:2729-2735, 1992.
  304. Sedegah, M., Chiang, C.H., Weiss, W.R., Mellouk, S., Cochran, M.D., Houghten, R.A., Beaudoin, R.L., Smith, D., Hoffman, S.L. Recombinant pseudorabies virus carrying a plasmodium gene: herpesvirus as a new live viral vector for inducing T- and B-cell immunity. Vaccine 10:578-84, 1992.
  305. Shirai, M., Akasuka, T., Pendleton, C.D., Houghten, R., Wychowski, C., Mihalik, K., Feinstone, S., Berzofsky, J.A. Induction of cytotoxic T cells to a cross-reactive epitope in the hepatitis C virus nonstructural RNA polymerase like protein. J. Virol. 66:4098-4106, 1992.
  306. Takahashi, H., Nakagawa, Y., Pendleton, C.D., Houghten, R.A., Yokomuro, K., Germain, R.N., Berzofsky, J.A. Analysis of CTL crossreactivity to an HIV-1 immunodominant determinant: elicitation of widely crossreactive CTL. In: Vaccines 92 (F. Brown, R.M. Chanock, H.S. Ginsberg, and R.A. Lerner, Eds.) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp.69-74, 1992.
  307. Takahashi, H., Nakagawa, Y., Pendleton, C.D., Houghten, R.A., Yokomuro, K., Germain, R.N., Berzofsky, J.A. Induction of broadly crossreactive cytotoxic T cells recognizing an HIV-1 envelope determinant. Science 255:333-336, 1992.
  308. Tsang, P., Rance, M., Fieser, T.M., Ostresh, J.M., Houghten, R.A., Lerner, R.A., Wright, P.E. Conformation and dynamics of an Fab'-bound peptide by isotope-edited NMR spectrocopy. Biochemistry 31:3862-3871, 1992.
  309. Weiss, W., Berzofsky, J.A., Houghten, R.A., Sedegah, M., Hollindale, M., Hoffman, S.L. A T cell clone directed at the circumsporozoite protein which protects mice against both Plasmodium yoelii and Plasmodium berghei. J. Immunol. 149:2103-2109, 1992.
  310. Zevering, Y., Amante, F., Smillie, A., Currier, J., Smith, G., Houghten, R.A., Good, M.F. High frequency of malaria-specific T cells in non-exposed humans. Eur. J. Immunol. 22:689-696, 1992.

  311. Berliner, S.A., Houghten, R.A., Roberts, J.R., Ruggeri, Z.M. Multiple Epitope specificity of monoclonal antibodies to a single synthetic peptide: Use in the characterization of the GP IIb-IIIa binding domain of Von Willebrand factor. In: Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis (C.Y. Liu and S. Chien, Eds.). Plenum Press, New York, pp. 133-144, 1991.
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  313. Blondelle, S.E., Houghten, R.A. Hemolytic and antimicrobial activities of the twenty-four individual omission analogues of melittin. Biochemistry 30:4671-4678, 1991.
  314. Blondelle, S.E., Houghten, R.A. Probing the relationships between the structure and hemolytic activity of melittin with a complete set of leucine substitution analogs. Pept. Res. 4:12-18, 1991.
  315. Büttner, K., Houghten, R.A. Induced conformations of peptides during RP-HPLC: Positional dependence of methionine oxidation. In: Peptides 1990: Proceedings of the 21st European Peptide Symposium (E. Giralt and D. Andreu, Eds.). ESCOM Science Publishers B.V., pp. 478-480, 1991.
  316. De Groot, A.S., Clerici, M., Hosmalin, A., Hughes, S.H., Barnd, D., Hendrix, C.W., Houghten, R.,Shearer, G.M., Berzofsky, J.A. Human immunodeficiency virus (HIV-1) reverse transcriptase T helper epitopes identified in mice and humans: correlation with a cytotoxic T cell (CTL) epitope. J. Infec. Dis. 164:1058-65, 1991.
  317. Doolan, D.L., Houghten, R.A., Good, M.F. Assessment of human cytotoxic T cell activity using synthetic peptides: Potential for field application. Peptide Res. 4(3):125-131, 1991.
  318. Doolan, D.L., Houghten, R.A., Good, M.F. Location of human cytotoxic T cell epitopes within a polymorphic domain of the Plasmodium falciparum circumsporozoite protein. Int. Immunol. 3:511-516,1991.
  319. Houghten, R.A., Ostresh, J.M., Pratt, S.M. Modified solid-phase methods for the rapid syntheis of opioid peptides. In: Emerging Technologies and New Directions in Drug Abuse Research, Research Monograph 112 (Rapaka, R., Makriyannis, A., and Kuhar, M.J., Eds.), National Institute on Drug Abuse, Rockville, MD, pp. 239-255, 1991.
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  321. Jezek, J., Houghten, R.A. A comparative study of BOP as a coupling agent using simultaneous multiple peptide synthesis (SMPS). In: Peptides 1990: Proceedings of the 21st European Peptide Symposium (E. Giralt and D. Andreu, Eds.). ESCOM Science Publishers B.V., pp. 74-75, 1991.
  322. Malik, A., Egan, J.E., Houghten, R.A., Sadoff, J.C., Hoffman, S.L. Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein. Proc. Natl. Acad. Sci. 88:3300-3304, 1991.
  323. Markoff, L.J., Innis, B.L., Houghten, R., Henchal, L.S. Development of cross-reactive antibodies to plasminogen during the immune response to dengue virus infection. J. Infect. Dis. 164:294-301, 1991.
  324. Mesters, R.M., Houghten, R.A., Griffin, J.H. Identification of a sequence of human activated protein C (residues 390-404) essential for its anticoagulant activity. J. Biol. Chem. 266:24514-24519, 1991.
  325. Milich, D.R., McLachlan, A., Raney, A.K., Houghten, R.A., Thornton, G.B., Maruyama, T., Hughes, J.L., Jones, J.E. Autoantibody production in hepatitis B e antigen transgenic mice elicited with a self T-cell peptide and inhibited with nonself peptides. Proc. Natl. Acad. Sci. 88:4348-4352, 1991.
  326. Ostresh, J.M., Büttner, K., Houghten, R.A. Reversed-phase chromatography: The effect of induced conformational effects on peptide retention. In: HPLC of Peptides and Proteins: Separation, Analysis, and Conformation (Mant, C. and Hodges, R.S., Eds.), CRC Press, Boca Raton, FL, pp. 633-642, 1991.
  327. Pinilla, C., Appel, J.R., Houghten, R.A. Peptide-monoclonal antibody interactions defined at the amino acid level: Advantages of competitive ELISA techniques. In: Peptides 1990: Proceedings of the 21st European Peptide Symposium (Giralt, E. and Andreu, D., Eds.), ESCOM Science Publishers B.V., Leiden, pp. 860-861, 1991.
  328. Revak, S.D., Merritt, T.A., Hallman, M., Heldt, G., La Polla, R.J., Hoey, K., Houghten, R.A., Cochrane, C.G. The use of synthetic peptides in the formation of biophysically and biologically active pulmonary surfactants. Pediatric Res. 29(5):460-465, 1991.

  329. Appel, J.R., Pinilla, C., Niman, H., Houghten, R.A. Elucidation of discontinuous linear determinants in peptides. J. Immunol. 144:976-983, 1990.
  330. Arad, O., Houghten, R.A. An evaluation of the advantages and effectiveness of picric acid monitoring during solid phase peptide synthesis. Peptide Res. 3:42-50, 1990.
  331. Büttner, K., Arad, O., Ostresh, J.M., Houghten, R.A. Amphipathic peptides: Synthesis, structural analysis and biological importance. In: Innovation & Perspectives in Solid Phase Synthesis (Epton, R., Ed.), Solid Phase Conference Coordination, Oxford, pp. 325-336, 1990.
  332. Büttner, K., Ostresh, J.M., Houghten, R.A. Induced conformational effects during RPHPLC: Prediction of immunodominant TH-cell antigenic sites. In: Proceedings of the 11th American Peptide Symposium (Rivier, J.E. and Marshall, G.R., Eds.), Escom Science Publishers B.V., The Netherlands, pp. 423-425, 1990.
  333. Cuervo, J.H., Rodriguez, B., Houghten, R.A. Synthesis and antimicrobial activity of magainin alanine substitution analogs. In: Peptides, Proceedings of the 11th American Peptide Symposium (J.E. Rivier and G. Marshall, Eds.). Escom Science Publishers B.V., The Netherlands, pp. 124-126, 1990.
  334. Foster, P.A., Fulcher, C.A., Houghten, R.A., Mahoney, S., Zimmerman, T.S. A murine monoclonal anti-Factor VIII inhibitory antibody and two human factor VIII inhibitors bind to different areas within a twenty amino acid segment of the acidic region of factor VIII heavy chain. Blood Coagulation and Fibrinolysis. 1:9-15, 1990.
  335. Foster, P.A., Fulcher, C.A., Houghten, R.A., Zimmerman, T.S. A synthetic factor VIII peptide of eight amino acid residues (1677-1684) contains the binding region of an anti-factor VIII antibody which inhibits the binding factor VIII to von Willebrand factor. Thrombosis and Haemostasis. 63(3):403-406, 1990.
  336. Foster, P.A., Fulcher, C.A., Houghten, R.A., Zimmerman, T.S. Synthetic factor VIII peptides with amino acid sequences contained within the C2 domain of factor VIII inhibit factor VIII binding to phosphatidylserine. Blood. 75(10):1999-2004, 1990.
  337. Good, M.F., Branigan, J., Smith, C., Houghten, R.A. Peptide immunization can elicit malaria protein-specific memory helper but not proliferative T cells. Peptide Res. 3:110-115, 1990.
  338. Hosmalin, A., Clerici, M., Houghten, R., Pendleton, C.D., Flexner, C., Lucey, D.R., Moss, B., Germain, R.N.,Shearer, G.M., Berzofsky, J.A. An epitope in human immunodeficiency virus 1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. 87:2344-2348, 1990.
  339. Huff, J.P., Roos, G., Peebles, C.L., Houghten, R., Sullivan, K.F., Tan, E.M. Insights into native epitopes of proliferating cell nuclear antigen using recombinant DNA protein products. J. Exp. Med. 172:419-429, 1990.
  340. Kim, J.E., Kojima, M., Houghten, R., Pendleton, C.D., Cornette, J.L., DeLisi, C., Berzofsky, J.A. Characterization of a helper T cell epitope recognized by mice of a low responder major histocompatibility type. Mol. Immunol. 27:941-946, 1990.
  341. Sikorska, M., Brewer, L.M., Youdale, T., Richards, R., Whitfield, J.F., Houghten, R.A., Walker, P.R. Evidence that mammalian ribonucleotide reductase is a nuclear membrane associated glycoprotein. Biochem. Cell Biol. 68:880-888, 1990.
  342. Tsang, P., Fieser, T.M., Ostresh, J.M., Houghten, R.A., Lerner, R.A., Wright, P.E. Solution NMR studies of Fab'-peptide complexes. In: UCLA Symposium Proceedings: Frontiers of NMR in Molecular Biology, Alan R. Liss, Inc., New York, pp. 63-73, 1990.
  343. Vicente, V., Houghten, R.A., Ruggeri, Z.M. Identification of a site in the alpha chain of platelet glycoprotein Ib that participates in von Willebrand factor binding. J. Biol. Chem. 265,1:274-280, 1990.
  344. Weiss, W.R., Houghten, R.A., Good, M.F., Berzofsky, J.A., Miller, L.H., Hoffman, S.L. A CTL epitope on the circumsporozoite protein of P. yoelii. Bull. World Health Organ. 68 Suppl:99-103, 1990.
  345. Weiss, W.R., Mellouk, S., Houghten, R.A., Sedegah, M., Kumar, S., Good, M.F., Berzofsky, J.A., Miller, L.H., Hoffman, S.L. Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria infected hepatocytes. J. Exp. Med. 171:49-58, 1990.
  346. Zevering, Y., Houghten, R.A., Frazer, I.H., Good, M.F. Major population differences in T cell response to malaria vaccine candidate. Int. Immunol. 2:945-955, 1990.

  347. Cadroy, Y., Houghten, R.A., Hanson, S.R. RGDV peptide selectively inhibits platelet-dependent thrombus formation in vivo. Studies using a baboon model. J. Clin. Invest. 84:939-944, 1989.
  348. Hale, P.M., Cease, K.B., Houghten, R.A., Ouyang, C., Putney, S., Javaherian, K., Margalit, H., Cornette, J.L., Spouge, J.L., DeLisi, C., Berzofsky, J.A. T cell multideterminant regions in the human immunodeficiency virus envelope: toward overcoming the problem of major histocompatibility complex restriction. Int. Immunol. 1:409-415, 1989.
  349. Hobbs, M.V., Houghten, R.A., Janda, J.A., Weigle, W.O., Morgan, E.L. Induction of human B cell differentiation by Fc region activators. I. Identification of an active tetrapeptide. Clin. Immunol. Immunopathol. 50:251-263, 1989.
  350. Houghten, R.A., Appel, J.R., Pinilla, C. The effects of induced conformational changes on the antigenicity and immunogenicity of synthetic branched peptides polymers. In: Peptides 1988 - Proceedings of the 20th European Peptide Symposium (Jung, G. and Bayer, E., Eds.), Walter de Gruyter & Co., Berlin, pp. 217-21, 1989.
  351. Houghten, R.A., Lynam, N. The rapid preparation of large numbers of discrete peptides for biological, immunological, and methodological studies: improved end-capping reagents. In: Peptides 1988: Proceedings of the 20th European Peptide Symposium (G. Jung and E. Bayer, Eds.). Walter de Gruyter & Co., Berlin, pp. 214-216, 1989.
  352. Hubenthal-Voss, J., Houghten, R.A., Roizman, B. Analysis of the functional and antigenic domains of the herpes simplex virus major regulatory protein a4. In: Synthetic Peptides: Approaches to Biological Problems. Alan R. Liss, Inc., pp. 239-254, 1989.
  353. Kinoshita, C.M., Ying, S.C., Hugli, T.E., Siegel, J.N., Potempa, L.A., Jiang, H., Houghten, R.A., Gewurz, H. Elucidation of a protease-sensitive site involved in the binding of calcium to C-reactive protein. Biochemistry 28:9840-9848, 1989.
  354. Mathiesen, T., Chiodi, F., Broliden, P.A., Albert, J., Houghten, R.A., Utter, G., Wahren, B., Norrby, E. Analysis of a subclass-restricted HIV-1 gp41 epitope by omission peptides. Immunol. 67:1-7, 1989.
  355. Milich, D.R., Hughes, J.L., Houghten, R., McLachlan, A., Jones, J.E. Functional identification of agretopic and epitopic residues within an HBcAg T cell determinant. J. Immunol. 143:3141-3147, 1989.
  356. Milich, D.R., Jones, J.E., McLachlan, A., Houghten, R., Thornton, G.B., Hughes, J.L. Distinction between immunogenicity and tolerogenicity among HBcAg T cell determinants. Influence of peptide-MHC interaction. J. Immunol. 143:3148-3156, 1989.
  357. Nemerow, G.R., Houghten, R.A., Moore, M.D., Cooper, N.R. Identification of an epitope in the major envelope protein of Epstein-Barr virus that mediates viral binding to the B lymphocyte EBV receptor (CR2). Cell 56:369-377, 1989.
  358. Norrby, E., Biberfeld, G., Johnson, P.R., Parks, D.E., Houghten, R.A., Lerner, R.A. The chemistry of site-directed serology for HIV infections. AIDS Res. Hum. Retrov. 5:473-479, 1989.
  359. Norrby, E., Parks, D.E., Utter, G., Houghten, R.A., Lerner, R.A. Immunochemistry of the dominating antigenic region of Ala582 to Cys604 in the transmembranous protein of simian immunodeficiency virus and human immunodeficiency virus. J. Immunol. 143:3602-3608, 1989.
  360. Takahashi, H., Cohen, J., Hosmalin, A., Cease, K.B., Houghten, R., Cornette, J.L., DeLisi, C., Merli, S., Germain, R.N., Moss, B., Berzofsky, J.A. Limited epitope repertoire recognized with class I MHC molecules by murine cytotoxic T lymphocytes on the HIV gp160 envelope glycoprotein. In: Vaccines 89 (R. Lerner, H. Ginsberg, R. Chanock and F. Brown, Eds.). Cold Spring Harbor, New York, pp. 109-114, 1989.
  361. Takahashi, H., Houghten, R., Putney, S.D., Margulies, D.H., Moss, B., Germain, R.N., Berzofsky, J.A. Structural requirements for Class I MHC molecule-mediated antigen presentation and cytotoxic T cell recognition of an immunodominant determinant of the human immunodeficiency virus envelope protein. J. Exp. Med. 170:2023-2035, 1989.
  362. Takahashi, H., Merli, S., Putney, S.D., Houghten, R., Moss, B., Germain, R.N., Berzofsky, J.A. A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. Science 246:118-121, 1989.
  363. Troye-Blomberg, M., Riley, E.M., Perlmann, H., Andersson, G., Larsson, A., Snow, R.W., Allen, S.J., Houghten, R.A., Olerup, O., Greenwood, B.M., Perlmann, P. T and B cell responses of Plasmodium falciparum malaria-immune individuals to synthetic peptides corresponding to sequences in different regions of the P. falciparum antigen Pf155/RESA. J. Immunol. 143:3043-3048, 1989.
  364. Voegtline, M.S., Houghten, R.A., Minden, P. Determination of antigenic binding sites in antibodies directed against a mycobacterial peptide by deletion and substitution of single amino acids. Peptide Res. 2:227-231, 1989.
  365. Young, E.A., Houghten, R.A., Akil, H. Degradation of [3H]ß-endorphin in rat plasma is increased with chronic stress. Eur. J. Pharm. 167:229-236, 1989.

  366. Berliner, S., Niiya, K., Roberts, J.R., Houghten, R.A., Ruggeri, Z.M. Generation and characterization of peptide-specific antibodies that inhibit von Willebrand factor binding to glycoprotein IIb-IIIa without interacting with other adhesive molecules: Selectivity is conferred by Pro1743 and other amino acid resid J. Biol. Chem. 263:7500-7505, 1988.
  367. Chersi, A., Morganti, M.C., Chillemi, F., Houghten, R., Cenciarelli, C. Generation of rabbit antipeptide antibodies to HLA-Class II antigens by the use of synthetic peptides. Clin. Exp. Immunol. 73:76-81, 1988.
  368. Clark, J.A., Houghten, R., Pasternak, G.W. Opiate binding in calf thalamic membranes: I. A selective MU1 binding assay. Mol. Pharm. 34:308-317, 1988.
  369. Cuervo, J.H., Rodriguez, B., Houghten, R.A. The Magainins: Sequence factors relevant to increased antimicrobial activity and decreased hemolytic activity. Peptide Res. 1:81-86, 1988.
  370. Dontfraid, F., Cochran, M.A., Pombo, D., Knell, J.D., Quakyi, I.A., Kumar, S., Houghten, R.A., Berzofsky, J.A., Miller, L.H., Good, M.F. Human and murine CD4 T-cell epitopes map to the same region of the malaria circumsporozoite protein: limited immunogenicity of sporozoites and circumsporozoite protein. Mol. Biol. and Med. 5:185-196, 1988.
  371. Dyson, H.J., Rance, M., Houghten, R.A., Lerner, R.A., Wright, P.E. Folding of immunogenic peptide fragments of proteins in water solution. I. Sequence requirements for the formation of a reverse turn. J. Mol. Biol. 201:161-200, 1988.
  372. Dyson, H.J., Rance, M., Houghten, R.A.