文章基本信息

标题：Antimicrobial effects of syndiotactic polypeptides
本地全文：下载
作者：Prakash Kishore Hazam ; Chimanjita Phukan ; R. Akhil 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2021
卷号：11
期号：1
页码：1823
DOI：10.1038/s41598-021-81394-2
出版社：Springer Nature
摘要：Abstract We present design and antibacterial studies of stereochemically diversified antimicrobial peptides against multidrug-resistant bacterial pathogens. Syndiotactic polypeptides are polymers of alternating L and D amino acids with LDLD or DLDL backbone stereochemical sequence, which can form stable gramicidin like helical conformations. We designed, synthesized and characterized eight model molecular systems with varied electrostatic fingerprints, modulated through calibrated sequence positioning. Six out of eight model systems showed very impressive antimicrobial activity against three difficult to treat bacterial species, Gentamicin resistant MRSA, E. coli and Mycobacterium. More importantly, the designed LDLD peptides were equally potent in serum, an important drawback of poly L peptide sequences due to enzyme mediated degradation and ion sensitivity. Further, we tested the activity of the designed peptides against drug-resistant clinical isolates of Staphylococcus aureus and Escherichia coli . Molecular dynamics simulation studies suggest formation of an assembly of individual peptides, preceding the membrane interaction and deformation. The activity estimates are comparable with the available peptide based antimicrobials, and are also highly specific and less toxic as per standard estimates. Incorporation of D amino-acids can significantly expand the peptide design space, which can in turn manifest in future biomaterial designs, especially antimicrobials.