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

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.

Hyphenation of liquid chromatography to ion trap mass spectrometry to identify minor components in polypeptide antibiotics

“…Which isomers correspond to the previously identified valine-polymyxin E 1 and E 2 could not be defined. One compound has already been synthesized by Kline et al [81]. The MS/MS spectrum and the first and second series of product ions for peak 5 are shown in Fig.…”

Synthesis and Bioactivity Investigation of the Individual Components of Cyclic Lipopeptide Antibiotics

“…Sakura et al estimated the antimicrobial activities of the synthetic polymyxins B 1 , B 2 , B 3 , B 4 , B 5 , B 6 , and B 1 -Ile . Kline et al synthesized and evaluated the in vitro antimicrobial activities of polymyxins E 1 , E 7 , and E 1 -Ile . However, too little is understood about the pharmacological differences between the individual constituents, especially their toxicity differences.…”

Magnetic Extraction of Acinetobacter baumannii Using Colistin-Functionalized γ-Fe2O3/Au Core/Shell Composite Nanoclusters

“…This interaction disrupts the outer membrane, and lipopolysaccharide is released . Masking the five primary amine groups on the lariat of the colistin molecule weakens the antibacterial activity . Therefore, it is presumed that positively charged amine groups in the lariat of the antibiotic play an important role in the interaction with the bacterial lipopolysaccharides as well as the bactericidal effects of the molecule at physiological pH .…”