Structure−Function Studies of Polymyxin B Nonapeptide:  Implications to Sensitization of Gram-Negative Bacteria#

摘要: Polymyxin B nonapeptide (PMBN), a cationic cyclic peptide derived by enzymatic processing from the naturally occurring polymyxin B, is able to increase permeability of outer membrane Gram-negative bacteria toward hydrophobic antibiotics probably binding bacterial lipopolysaccharide (LPS). We have synthesized 11 analogues PMBN and evaluated their activities compared that PMBN. The synthetic peptides were much less potent than in capacity sensitize Escherichia coli Klebsiella pneumoniae novobiocin displace dansyl-PMBN LPS. Moreover, unlike PMBN, none inhibit growth Pseudomonas aeruginosa. structural-functional features characterized identified with regard ring size, distance between positive charges backbone, chirality DPhe-Leu domain, nature charged groups. Apparently, structure highly specific for efficient perturbation as well LPS binding. present study further increases our understanding complex PMBN-LPS may, potentially, enable design compounds having enhanced permeabilization potency membrane.