Open AccessN-Terminal Fatty Acid Substitution Increases the Leishmanicidal Activity of CA(1-7)M(2-9), a Cecropin-Melittin Hybrid Peptide
Author(s) -
Carmen Chicharro,
Cesare Granata,
Raquel García Lozano,
David Andreu,
Luís Rivas
Publication year - 2001
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.45.9.2441-2449.2001
Subject(s) - melittin , peptide , acylation , biochemistry , chemistry , fatty acid , cecropin , lysine , residue (chemistry) , amino acid , antimicrobial peptides , catalysis
In order to improve the leishmanicidal activity of the synthetic cecropin A-melittin hybrid peptide CA(1-7)M(2-9) (KWKLFKKIGAVLKVL-NH(2)), a systematic study of its acylation with saturated linear fatty acids was carried out. Acylation of the N(epsilon)-7 lysine residue led to a drastic decrease in leishmanicidal activity, whereas acylation at lysine 1, in either the alpha or the epsilon NH(2) group, increased up to 3 times the activity of the peptide against promastigotes and increased up to 15 times the activity of the peptide against amastigotes. Leishmanicidal activity increased with the length of the fatty acid chain, reaching a maximum for the lauroyl analogue (12 carbons). According to the fast kinetics, dissipation of membrane potential, and parasite membrane permeability to the nucleic acid binding probe SYTOX green, the lethal mechanism was directly related to plasma membrane permeabilization.