Dissociation of antibacterial and hemolytic activities of an amphipathic peptide antibiotic.

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Qin C, Zhong X, Bu X, Ng NL, Guo Z

Dissociation of antibacterial and hemolytic activities of an amphipathic peptide antibiotic.

J Med Chem. 2003 Nov 6;46(23):4830-3. doi: 10.1021/jm0341352.

PubMed ID
14584933 [ View in PubMed
]
Abstract

Using an alanine-scanning method, we have found that the antibacterial and hemolytic activities of the amphipathic cyclic decapeptide antibiotic tyrocidine A depend on different structural components. Single substitution of glutamine-6 of the natural product with a cationic amino acid results in a therapeutic index enhancement of up to 140-fold. Successful dissociation of the two intimately associated properties should enable discovery of novel analogues with both high bacterial selectivity and antibacterial potency to counter microbial resistance.

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