ORGN 2 |
| The emergence of pathogenic bacteria with clinically significant resistance to conventional antibiotics is a major public health concern. The development of a new class of antibiotics has become critical. The designed cationic antimicrobial peptides whose sole target is the cytoplasmic membrane could represent such a class since the development of resistance is not expected because this would require substantial changes in the lipid composition of the cell membranes of microorganisms. Utilizing a structure-based rational approach to antimicrobial peptide design in two structural classes of peptides (cyclic beta-sheet and alpha-helical) we were able to develop antimicrobial peptides with improved activity, specificity and clinical potential as broad spectrum antibiotics. The controlled disruption of beta-sheet and alpha-helical structure (disruption under benign conditions and inducible in hydrophobic conditions) is related to strong antimicrobial activity over a variety of Gram-negative and Gram-positive bacterial strains and specificity to human cells (no detectable hemolytic activity). These results have led to a new proposed mechanism of action of antimicrobial peptides in biomembranes. |
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Ralph F. Hirschmann Award in Peptide Chemistry
8:00 AM-12:00 PM, Sunday, 13 March 2005 Convention Center -- Ballroom 20A-B, Oral
Division of Organic Chemistry |