Synthesis and characterization of the colistin peptide polymyxin E1 and related antimicrobial peptides


  • To cite this article:

    Kline, T., Holub, D., Therrien, J., Leung, T. & Ryckman, D. Synthesis and characterization of the colistin peptide polymixin E1 and related antimicrobial peptides.

    J. Peptide Res., 2001, 57, 175–187.

T. Kline
PathoGenesis Corporation
201 Elliott Avenue West
WA 98119
Tel.: +1-206-505-6914
Fax: +1-206-282-5065


Abstract: Two strategies were developed to synthesize the acylated cyclic peptides know as polymyxins. Synthesis of polymyxin E1 and several analogs enabled us to evaluate the minimum inhibitory concentration of individual compounds against Gram-negative bacteria. In this study we also report the first identification of two component peptides in the complex polymyxin fermentation product colistin, a Thr2Ser isoform and an acyl group isomer. Both of these peptides, as well as a known component peptide, Leu7Ile, were similar to polymyxin E1 in potency, suggesting that conservative mutations in the colistin family are functionally inconsequential. In contrast, the acyclic analogs of all of these peptides were inactive, indicating that the characteristic lariat structure of the polymyxins is necessary for antimicrobial activity.