title: Structure-function relationship studies on the frog skin antimicrobial peptide tigerinin 1: design of analogs with improved activity and their action on clinical bacterial isolates.
abstract: Structure-function relationships in antimicrobial peptides have been extensively investigated in order to obtain improved analogs. Most of these studies have targeted either alpha-helical peptides or beta-sheet peptides with multiple disulfide bridges. Tigerinins are short, nonhelical antimicrobial peptides with a single disulfide bridge. In this study, we have synthesized several analogs of tigerinin 1 with an aim to understand the structural basis of activity as well as improve its activity. The studies demonstrate that the loop structure of tigerinin 1 is essential for its optimal activity. However, linearization with increased cationic charges can compensate for loss of loop structure to some extent. Morphology of the cells after treatment with the active analogs shows extensive leakage of cytoplasmic contents. Tigerinin 1 and two of its analogs exhibit impressive activity against a variety of clinical bacterial isolates.
authors.affiliation: Center for Cellular and Molecular Biology, Hyderabad 500 007, India. sitaram@gene.ccmbindia.org
authors.forename: Narasimhaiah
authors.initials: N
authors.lastname: Sitaram
authors.forename: Korrapati Purna
authors.initials: KP
authors.lastname: Sai
authors.forename: Shashi
authors.initials: S
authors.lastname: Singh
authors.forename: Krishnan
authors.initials: K
authors.lastname: Sankaran
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Nagaraj
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001419:Bacteria / Q000187:drug effects*; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D010455:Peptides / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C469876:tigerinin 1