Decoralin Analogs with Increased Resistance to Degradation and Lower Hemolytic Activity

Abstract

Abstract Decoralin is an antimicrobial peptide with activity against microorganisms and pronounced hemolytic activity. Decoralin analogs have been proposed, and the results indicated that when isoleucine at position 6 was substituted by phenylalanine residue, the peptides exhibited increased resistance towards enzymes action. Besides that, lower hemolytic activity was obtained for [Pro] 4 ‐Decoralin‐NH 2 and [Phe] 6 ‐Des[Thr] 11 ‐Decoralin‐NH 2 ; this effect is probably due to their poor helical tendency. [Arg] 1 ‐Decoralin‐NH 2 exhibited +4 net charge and lower hemolytic activity (25.0 μmol L −1 ) and even showed helical propensity; as a consequence, it presented the higher therapeutic indexes (values from 16.0 to 32.0). The helical conformational tendency is believed to be determinant of the antimicrobial activity of this decoralin family and has been shown to be as important as the increased positive net charge. This points to a new direction for the design of potential chemotherapeutic agents.