D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides.

Here we designed and synthesized analogs of two antimicrobial peptides, namely C10:0-A2, a lipopeptide, and TA4, a cationic α-helical amphipathic peptide, and used non-proteinogenic amino acids to improve their therapeutic properties. The physicochemical properties of these analogs were analyzed, including their retention time, hydrophobicity, and critical micelle concentration, as well as their antimicrobial activity against gram-positive and gram-negative bacteria and yeast. Our results showed that substitution with D- and N-methyl amino acids could be a useful strategy to modulate the therapeutic properties of antimicrobial peptides and lipopeptides, including enhancing stability against enzymatic degradation.

A Comparative Study of the Antimicrobial and Structural Properties of Short Peptides and Lipopeptides Containing a Repetitive Motif KLFK.

Background: In the last years, Antimicrobial Peptides (AMPs) and lipopeptides have received attention as promising candidates to treat infections caused by resistant microorganisms.

Objective: The main objective of this study was to investigate the effect of repetitive KLFK motifs and the attachment of aliphatic acids to the N-terminus of (KLFK)n peptides on therapeutic properties.

Methods: Minimal inhibitory concentration against Gram (+) and (-) bacteria and yeast of synthetic compounds were determined by broth microtiter dilution method, and the toxicity was evaluated by hemolysis assay.

Biological and structural effects of the conjugation of an antimicrobial decapeptide with saturated, unsaturated, methoxylated and branched fatty acids.

The increasing bacterial resistance against conventional antibiotics has led to the search for new antimicrobial drugs with different modes of action. Cationic antimicrobial peptides (AMPs) and lipopeptides are promising candidates to treat infections because they act on bacterial membranes causing rapid destruction of sensitive bacteria. In this study, a decapeptide named A2 (IKQVKKLFKK) was conjugated at the N-terminus with saturated, unsaturated, methoxylated and methyl -branched fatty acids of different chain lengths (C8 - C20), the antimicrobial and structural properties of the lipopeptides being then investigated.