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The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin‐L
Author(s) -
Buommino Elisabetta,
Carotenuto Alfonso,
Antignano Ignazio,
Bellavita Rosa,
Casciaro Bruno,
Loffredo Maria Rosa,
Merlino Francesco,
Novellino Ettore,
Mangoni Maria Luisa,
Nocera Francesca Paola,
Brancaccio Diego,
Punzi Pasqualina,
Roversi Daniela,
Ingenito Raffaele,
Bianchi Elisabetta,
Grieco Paolo
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900221
Subject(s) - pyrrolidine , antimicrobial , circular dichroism , stereochemistry , proline , chemistry , cytotoxicity , antimicrobial peptides , structure–activity relationship , glutamine , peptide , combinatorial chemistry , amino acid , biochemistry , organic chemistry , in vitro
Previously, we identified a potent antimicrobial analogue of temporin L (TL), [Pro 3 ]TL, in which glutamine at position 3 was substituted with proline. In this study, a series of analogues in which position 3 is substituted with non‐natural proline derivatives, was investigated for correlations between the conformational properties of the compounds and their antibacterial, cytotoxic, and hemolytic activities. Non‐natural proline analogues with substituents at position 4 of the pyrrolidine ring were considered. Structure–activity relationship (SAR) studies of these analogues were performed by means of antimicrobial and cytotoxicity assays along with circular dichroism (CD) and NMR spectroscopic analyses for selected compounds. The most promising peptides were additionally evaluated for their activity against some representative veterinary microbial strains to compare with those from human strains. We identified novel analogues with interesting properties that make them attractive lead compounds.