Faculty · Staff · Graduate Students

Lenore M. Martin

Research Interests:

Combinatorial Libraries, Antimicrobial Peptide Chemistry, Analytical Biochemistry, Bioinformatics, and Structural Biology. We investigate the complex interactions between biopolymers (peptides, proteins, DNA, RNA, lipids, and carbohydrates) in order to understand cellular physiology at the molecular level. My research at URI has focussed on using solid-phase peptide synthesis (SPPS) to prepare diverse combinatorial libraries of both naturally-occurring and engineered peptides for further study. We have designed antimicrobial peptides (AMPs) based upon pleurocidin, isolated from Winter Flounder, to combat the growing problem of antimicrobial resistance in pathogenic microbes, and topoisomerase inhibitors based on natural products for use in cancer chemotherapy. Our bioanalytical chemistry research has involved the development of novel methods for monitoring dynamic properties of peptides, proteins, lipids and DNA using capillary electrophoresis (CE), circular dichroism (CD), and nuclear magnetic resonance (NMR) spectroscopy. The molecular modeling/bioinformatics research area aims to expand the application of molecular mechanics techniques in order to model dynamic processes in the biopolymers we investigate.

Before we began our research, most peptide-type natural products had not been prepared using solid-phase peptide synthesis, usually because the appropriate amino acids were not commercially available. To address this problem, my first graduate student, Bi-Huang Hu and I designed and synthesized a series of amino acid building blocks that could be used to prepare natural products using solid-phase techniques. To demonstrate the utility of our building blocks, we used them to synthesize and active fragment of the naturally occurring antibiotic, microcin B17, on the solid phase. Microcin B17 is a remarkable peptide antibiotic secreted by Enterobacteriaceae of fecal origin, and in 1991, microcin B17 was identified as the first known peptide to inhibit a type II DNA topoisomerase. We proceeded to use our building blocks to generate a combinatorial library of novel thiazole and oxazole-containing biomimetic peptides, an after screening the resulting compounds for cytotoxic activity, suing a variety of cell types, we have discovered that many of the compounds in the library are selectively active against Saccharomyces cerevisiae, a common fungus.

The overall goal of the research program in the Martin Lab is to improve our understanding of clinically and agriculturally important biological processes through the use of synthetic organic and analytical chemistry approaches. The general approach in designing peptide probes, is to analyze the structure of a target protein or of a group of functionally related peptides, seeking a common motif in the naturally-occurring substance(s). When a suitable motif is identified, we then synthesize a model peptide or library of related peptides in our laboratory using solid-phase synthesis and/or combinatorial chemistry. Once adequate quantities of the model compounds are in hand, we have been able to study their behavior as they interact with biological systems such as cell extracts, lipid vesicles, and cell cultures. The application of our basic research program to the biotechnology industry include facilitating the large-scale production of biologically active natural products, and developing novel classes of antibiotic peptidomimetics that have been found to inhibit topoisomerase enzymes, a possible method of killing viruses, bacteria, fungi and cancer cells. The CE-based methods for monitoring biological processes also have many applications in pharmaceutical research and discovery.

Articles:

• Martin, Lenore M. Elsaid, Khaled A.; Dorrington, Tarquin; and Gómez-Chiarri, Marta. (2002) "Synthetic Studies on the Antimicrobial Activity of Pleurocidin" in Peptides: The Wave of the Future Houghten, Richard A.; Lebl, Michal; Fields, Gregg B.; and Barany, George eds., Kluwer Academic Publishers, Dordrecht, The Netherlands,pp. 475-476.
• Martin, Lenore M.; Messmer, Bradley; Thaler, David (2000) “Synthetic Peptide Analogs Compared with Phage Display” in Peptides for the New Millennium Gregg B. Fields, James P. Tam, and George Barany, eds., Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 172-73.
• Hu, Bi-Huang; Martin, Lenore M. (2000) “Design, Synthesis and Antibacterial Activity of a Peptidomimetic Library” in Peptides for the New Millennium Gregg B. Fields, James P. Tam, and George Barany, eds., Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 746-47.
• Martin, Lenore M. and Hu, Bi-Huang. (1999) “Thiazole and Oxazole Building Blocks for Combinatorial Synthesis” Tetrahedron Letters, 40; pp. 7951-53.
• Martin, Lenore M. “Design of Biomimetic Peptides for Antibiotic Use” (1999) In Maritimes: Environmental Biotechnology , 41(2) Bradley, T. Ed. URI Office of Marine Programs, Summer 1999; pp. 19-21.
• Li, Chunze; Martin, Lenore M. (1998) “A Robust Method for Determining DNA Binding Constants Using Capillary Zone Electrophoresis” Analytical Biochemistry. 263; pp. 72-78.
• Martin, Lenore M. (1996) “Facile Reduction in the Synthesis of Phosphorylcholine Affinity Columns” Tetrahedron Letters, 37(44); pp. 7921-24.
• Martin, Lenore M. (1996) “Antibody Fragment Separations by Capillary Zone Electrophoresis” Journal of Chromatography B. 675: pp. 17-25.
• Martin, Lenore M., Hu, Bi-Huang, and Li, Chunze (1998) “Enantiomeric Structural Libraries of Unnatural Peptides Which Bind DNA and Alter Enzymatic Activity” In Peptides: Frontiers of Peptide Science, Tam, J.P. and Kaumaya, P.T.P. eds), Kluwer Academic Publishing: Dordrecht, The Netherlands; pp. 122-23.
• Martin, Lenore M. (1996) “The Use of Ion-Pairing Reagents Improves the Separation of Hydrophobic Peptides by Capillary Electrophoresis” In Peptides: Chemistry, Structure and Biology; Kaumaya, P.T.P.; Hodges, R.; Eds.; Mayflower: England; pp. 144-45.
• Martin, Lenore M.; Rotondi, Kenneth S; Merrifield, R.B. (1994) “McPC603 VH(1-115): Synthesis and
  Folding of Immunoglobulin Variable Regions”, In Peptides: Chemistry and Biology; Hodges, R.; Smith, John A.; Eds.; ESCOM: Leiden; pp. 745-47.
• Martin, Lenore M.; Rotondi, Kenneth S; Merrifield, R.B. (1994) “Antibody Binding Constants by Capillary Electrophoresis”, In Peptides: Chemistry and Biology; Hodges, R.; Smith, John A.; Eds.; ESCOM: Leiden; pp. 249-51.
• Martin, Lenore M.; Merrifield, R.B. (1992) “Synthesis and Characterization of Immunoglobulin Variable Region Heavy and Light Chain Fragments” In Peptides: Chemistry and Biology; Smith, John A.; Rivier, Jean E. Eds.; ESCOM: Leiden; pp. 849-50.

Books:

Martin, Lenore M.; Scovell, William (2003) Student Study Guide & Problems Book for Campbell & Farrell’s Biochemistry 4^th ed. Chapters 7-21. Brooks/Cole, Thomson Learning Inc. 454 pages. ISBN 0-03-034917-6.

Hu, Bi-Huang; Martin Lenore M. (1999) “Capillary Electrophoresis of Peptides and Proteins” Chapter 4 in High-Resolution Chromatography: A Practical Approach, Millner, P.A. Ed. IRL/Oxford University Press: Oxford; pp. 77-116. ISBN 0-19-963648-6.

My Research Students
 

Mr. Khaled Elsaid - M.S. 2002

Phage Library Collaborators Meeting at The Rockefeller University

Displaying result of latest total synthesis of a natural product - Leah Elizabeth Ribner-Martin - Born February 20, 2001- at the 17th American / 2nd International peptide Symposium in San Diego, CA June 2001.