A potent antibacterial activity of new short d-enantiomeric lipopeptide against multi drug resistant bacteria

Publication date: Available online 26 October 2018Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Jaeho Lee, Shanghyeon Kim, Ji-Yeong Sim, Daeun Lee, Ha Hyung Kim, Jae Sam Hwang, Dong Gun Lee, Zee-Yong Park, Jae Il KimAbstractThe emergence of drug-resistant pathogenic bacteria threatens human health. Resistance to existing antibiotics is increasing, while the emergence of new antibiotics is slowing. Cationic antimicrobial peptides (CAMPs) are fascinating alternative antibiotics because they possess a broad spectrum of activity, being active against both Gram-positive and Gram-negative bacteria including those resistant to traditional antibiotics. However, low bioavailability resulting from enzymatic degradation and attenuation by divalent cations like Mg2+ and Ca2+ limits their use as antibiotic agents. Here, we report the design of new CAMPs showing both high antibacterial activity and serum stability under physiological ion concentrations. The peptides were designed by applying two approaches, the use of d-enantiomer and lipidation. Based on the sequence of the CopW (LLWIALRKK-NH2), a nonapeptide derived from coprisin, a series of novel d-form CopW lipopeptides with different acyl chain lengths (C6, C8, C10, C12, C14, and C16) were synthesized and evaluated with respect to their activity and salt sensitivity. Among the analogs, the d-form lipopeptide dCopW3 exhibited MIC values ranging from 1.25 to 5 μM against multidrug-resistant bacteria. Significa...
Source: Biochimica et Biophysica Acta (BBA) Biomembranes - Category: Biochemistry Source Type: research