Solid-phase peptide synthesis.
Hydrophobic matching of lipids and peptides.
Anchor functions of tryptophan at the membrane/water interface.
Folding and association of peptides within membranes.
Structure-activity analysis of cationic, tryptophan-rich antimicrobial peptides
A dramatic increase in multidrug resistant bacteria in recent years, along with a shortage of new antimicrobial agents, has led to a growing need to understand the properties of natural antimicrobial peptides and their mechanisms of action. Antimicrobial peptides, produced in all animal kingdoms (Bowman, 1995) and vital for the innate immune response, have considerable potential as new antibiotic drug candidates against the increasingly prevalent multiresistant pathogens. Unlike conventional antibiotics that target specific proteins, these peptides exert their effect directly on the cellular membrane lipids. Lactoferricin B is a 25-residue peptide with potent broad-spectrum antibiotic and antitumor activities that is released by pepsin from the N-terminal region of bovine lactoferrin. A smaller amidated peptide, lactoferricin B 20-25 (Arg-Arg-Trp-Gln-Trp-Arg-NH2), retains significant activity, suggesting that it may constitute a core active region or perhaps even the “antimicrobial active-site.” Although the tryptophan and arginine residues are essential for biological activity, the molecular details of the lipid interactions remain unclear.
In our lab we use solid phase methods to synthesize sequence modified and site-specifically labeled analogues of lactoferricin B 20-25. The structures of the modified peptides are analyzed by solution and solid state NMR spectroscopy, and their antimicrobial activity is assayed. Using this structure-based design approach, we hope to develop new and broadly applicable methods to facilitate structural analysis of amphipathic antimicrobial peptides and to enhance their efficacy as antimicrobial agents.
Ph.D., University of Arkansas
B.A., University of Colorado, Colorado Springs