A repertoire of novel antibacterial diastereomeric peptides with selective cytolytic activity.

The Journal of Biological Chemistry
Z OrenY Shai

Abstract

The increase in infectious diseases and bacterial resistance to antibiotics has resulted in intensive studies focusing on the use of linear, alpha-helical, cytolytic peptides from insects and mammals as potential drugs for new target sites in bacteria. Recent studies with diastereomers of the highly potent cytolytic peptides, pardaxin and melittin, indicate that alpha-helical structure is required for mammalian cells lysis but is not necessary for antibacterial activity. Thus, hydrophobicity and net positive charge of the polypeptide might confer selective antibacterial lytic activity. To test this hypothesis, a series of diastereomeric model peptides (12 amino acids long) composed of varying ratios of leucine and lysine were synthesized, and their structure and biological function were investigated. Peptide length and the position of D-amino acids were such that short peptides with stretches of only 1-3 consecutive L-amino acids that cannot form an alpha-helical structure were constructed. Circular dichroism spectroscopy showed that the peptides do not retain any detectable secondary structure in a hydrophobic environment. This enabled examination of the sole effect of hydrophobicity and positive charge on activity. The data r...Continue Reading

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Citations

May 20, 1999·Biopolymers·D Andreu, L Rivas
Nov 9, 2000·Journal of Peptide Science : an Official Publication of the European Peptide Society·L Otvos
Dec 20, 2002·Biopolymers·Yechiel Shai
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