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Predrag Cudic

Predrag_Cudic TorreyPinesInstituteFL
Associate Member
Bioorganic Chemistry
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Dr. Cudic's primary research interest is in the broadly defined field of bioorganic chemistry. His current research includes the design and preparation of multifunctional nanomedicine systems for effective cancer treatment, and novel drug discovery based on nonribosomal peptide natural products.

Multifunctional nanomedicines for targeting and detection of cancer cells (General Cancer Research)

The majority of human tumors originate from epithelial cells, and their development becomes apparent when tumor cells exfoliate spontaneously into saliva, urine, or blood. The molecular and genetic abnormalities within these tumor cells could be used to detect and identify precancerous lesions or very early stage cancers, as well as target for a selective anticancer therapy. One such abnormality is the change in carbohydrate expression on the cancer cell surface at the onset and during the progression of cancer. For example, overexpression of the sialylated Lewis oligosaccharide antigens, sLex and sLea, is highly correlated with tumor progression and metastatic spread, and leads to a poor clinical prognosis. In addition, it is well documented that sialyl Lewis antigens are ligands for E-selectin, an endothelial cell adhesion molecule. E-selectin participates in the adhesion of leukocytes and cancer cells to endothelial cells. It has long been recognized that inflammation is associated with the development of cancer, however, only recently has it been demonstrated that the tumor microenvironment shows similarity to a site of inflammation. Several types of tumor cells express functional selectin ligands and they may metastasize by a process that exploits the same selectin-dependent mechanisms used by migrating leukocytes during leukocyte trafficking. For these reasons, the interaction between E-selectin and sialyl Lewis antigens represents a particularly attractive target to interfere with metastasis-associated cancer cell adhesion. In addition, the changes in glycosylation that accompany the transformation of healthy cells to cancer cells could also be used for targeted delivery of cytotoxic drugs and/or imaging agents.

Nonribosomal peptide natural products (Drug Discovery):

Naturally occurring cyclic depsipeptides are peptides that contain one or more ester bonds in addition to the amide bonds, and they have emerged as an important source of pharmacologically active compounds and promising lead structures for the development of novel synthetically derived drugs. This class of natural products is present in many organisms, such as fungi, bacteria, and marine organisms. It is well known that cyclic depsipeptides and their derivatives exhibit a diverse spectrum of biological activities, including insecticidal, antiviral, antimicrobial, antitumor, carcinogenic, anti-inflammatory, and immunosuppressive actions. However, they have shown the greatest therapeutic potential as anticancer and antimicrobial agents. Exploitation of cyclic depsipeptides as lead compounds for development of new drugs has been hampered by difficulties associated with isolation and purification of larger quantities of this class of natural products, and by the lack of synthetic analogs. As an alternative, we use total solution or solid-phase peptide synthesis of these important natural products, as well as combinatorial chemistry approaches to elucidate structure–activity relationships and to find new potent compounds of this class.

Dr. Predrag Cudic earned his B.S. degree in Chemistry from the University of Zagreb, College of Science, Croatia, in 1991. He than pursued doctoral studies at the Rudjer Boskovic Institute, University of Zagreb, under the supervision of Prof. Mladen Zinic. Dr. Cudic's dissertation research at the Rudjer Boskovic Institute was directed toward design and synthesis of phenanthridinium cyclo-bis-intercaland receptor molecules. This research resulted in synthesis of artificial receptor molecules capable of binding and recognition of nucleosides and nucleotides in water. In September 1996 Predrag obtained his Ph.D. degree in Organic Chemistry, and soon he joined group of Prof. Jean-Marie Lehn, 1987 Nobel Laureate in Chemistry, at the Collège de France in Paris, France, as a Postdoctoral Research Associate. In Prof. Lehn's Laboratory Dr. Cudic was engaged in the synthesis of acridine macrocyclic receptor molecules, investigation of molecular recognition by these receptors and their application in the catalysis of thermal and photochemical processes of organic and bioorganic interest.

In 1998 Dr. Cudic moved to USA where he obtained further training in the bioorganic chemistry field. He joined group of Prof. Dewey McCafferty at the University of Pennsylvania, School of Medicine, Philadelphia, as a Postdoctoral Research Associate. At the University of Pennsylvania Dr. Cudic's research was focused on the total solid-phase synthesis of a novel peptide antibiotic Ramoplanin, its mechanism of action and structure-activity relationship.

Starting in the August 2003, Dr. Cudic began his research and teaching career as an Assistant Professor at Florida Atlantic University in the Department of Chemistry and Biochemistry, and in August 2009 he was awarded tenure and promoted to the rank of Associate Professor. His research interests at FAU were focused on the design and synthesis of biomimetic carbohydrate receptors, and solid-phase synthesis and biological evaluation of nonribosomal peptide natural products.

In August 2010, he joined Torrey Pines Institute for Molecular Studies in Florida as Associate Member.

Education

  • 1987-1991      Bachelor of Science, University of Zagreb, Faculty of Science, Zagreb, Croatia
  • 1991-1996      Ph.D. in Organic Chemistry, University of Zagreb, Rudjer Boskovic Institute, Zagreb, Croatia

Positions

  • 1991-1996       Research Associate, Rudjer Boskovic Institute, University of Zagreb, Croatia
  • 1996-1998       Postdoctoral Fellow, College of France, France (Laboratory of Professor Jean-Marie Lehn, 1987 Nobel Laureate in Chemistry)
  • 1998-2003       Postdoctoral Fellow, University of Pennsylvania, School of Medicine, Philadelphia, PA (Laboratory of Professor Dewey G. McCafferty, currently at Duke University)
  • 2003-2009       Tenure-Track Assistant Professor, Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL
  • 2005-2010       Graduate Faculty, C. E. Schmidt College of Science, Florida Atlantic University, Boca Raton, FL
  • 2006                Member, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL
  • 2007-2010       Adjunct Assistant Professor, Department of Basic Science, College of Biomedical Science, Florida Atlantic University, Boca Raton, FL
  • 2009-2010       Tenured Associate Professor, Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL
  • 2010-present   Associate Member, Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL

Professional Affiliations

  • 2004                  Mail in Reviewer for the National Science Foundation (NSF), including Faculty Early Career Development (CAREER) Program
  • 2004                  Mail in Reviewer for the Oak Ridge Associated Universities (ORAU) Junior Faculty Proposals
  • 2004-present    Manuscript reviewer for Tetrahedron Letters, Journal of Biological Chemistry, Biochemistry, Bioorganic and Medicinal Chemistry Letters, Medicinal Chemistry, Chemical Biology and Drug Design, Biopolymers: Peptide Science, Organic Letters, Key Opinions, Journal of Medicinal Chemistry
  • 2005                  Book review, Practical Techniques and Experiments for the Biochemical Laboratory, Houghton Mifflin Company
  • 2009                  Mail in Reviewer for the National Institutes of Health (NIH), Recovery Act Limited Competition: NIH Challenge Grants in Health and Science Research (RC1)
  • 2009-present    American Peptide Society Newsletter Editor

Honors & Awards

  • 1989-1991                   Rudjer Boskovic Institute Scholarship, University of Zagreb, Croatia
  • 1996-1997                   French Government Scholarship

Selected Publications (10 of 36)

  1. A. A. Mensah, R. P. Cudic, 1,8-naphthiridine Based Artificial Receptors for Selective Monosaccharide Binding in Water, Current Organic Chemistry (2010), accepted.
  2. N. Bionda, M. Cudic, L. Barisic, M. Stawikowski, R. Stawikowska, D. Binetti, P. Cudic, A Practical Synthesis of Nα-Fmoc Protected L-threo-β-hydroxyaspartic acid Derivatives for Coupling via α- or β-Carboxylic Group, Amino Acids (2010) published online first, 1.
  3. N. Bionda, P. Cudic, Cyclic lipodepsipeptides in novel antimicrobial drug discovery, Croat. Chem. Acta. (2010), submitted.
  4. M. Cassone, P. Vogiatzi, R. La Montagna, V. Inacio, P. Cudic, J. Rux, L. Otvos, J. Wade, Scope and Limitations of the Designer Proline-rich Antibacterial Peptide Dimer, A3-APO, Alone or in Synergy with Conventional Antibiotics, Peptides 29 (2008) 1878.
  5. P. Cudic, M. Stawikowski, Pseudopeptide Synthesis via Fmoc Solid-Phase Synthetic Methodology, Mini. Rev. Org. Chem. 4 (2007) 268.
  6. L. Otvos, Jr., V. De Olivier Inacio, J. D. Wade, P. Cudic, Prior Antibacterial Peptide-Mediated Inhibition of Protein Folding in Bacteria Mutes Resistance Enzymes, Antimicrob. Agents Chemother. 50 (2006), 3146.
  7. M. Stawikowski and P. Cudic, A Novel Strategy for the Solid-phase Synthesis of Cyclic Lipodepsipeptides, Tetrahedron Lett. 47 (2006) 8587.
  8. P. Cudic, J. K. Kranz, D. C. Behenna, R. G. Kruger, H. Tadesse, Y. I. Veklich, J. W. Weisel, A. J. Wand, D. G. McCafferty, Complexation of Peptidoglycan Intermediates by the Lipoglycodepsipeptide Antibiotic Ramoplanin: Minimal Structural Requirements for Intermolecular Complexation and Fibril Formation, Proc. Nat. Acad. Sci. USA 99 (2002) 7384.
  9. P. Cudic, D. C. Behenna, J. K. Kranz, R. G. Kruger, A. J. Wand, Y. I. Veklich, J. W. Weisel, D. G. McCafferty, Functional Analysis of the Lipoglycodepsipeptide Antibiotic Ramoplanin, Chem. Biol. 9 (2002) 897.
  10. P. Cudic, J. P. Vigneron, J. M. Lehn, M. Cesario. T. Prange, Molecular Recognition of Azobenzene Dicarboxylate by Acridine-based Receptor Molecules. Crystal Structure of the Supramolecular Inclusion Complex of trans-3,3’-Azobenzene Dicarboxylate with Cyclo-bis-intercaland receptor, Eur. J. Org. Chem. (1999) 2479.

    P. Cudic, Artificial carbohydrate receptors and methods of use thereof, (2010), Pub. No.: WO/2010/005737, International application No.: PCT/US2009/047544