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Antimicrobial Agents and Chemotherapy, September 2001, p. 2441-2449, Vol. 45, No. 9
Centro de Investigaciones Biológicas
(CSIC), Velázquez 144, 28006 Madrid,1 and
Departament de Química Orgànica, Universitat de
Barcelona, Martí i Franquès 1, 08028 Barcelona,2 Spain
Received 16 February 2001/Returned for modification 18 April
2001/Accepted 5 June 2001
In order to improve the leishmanicidal activity of the synthetic
cecropin A-melittin hybrid peptide CA(1-7)M(2-9)
(KWKLFKKIGAVLKVL-NH2), a systematic study of its acylation
with saturated linear fatty acids was carried out. Acylation of the
N
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.9.2441-2449.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
N-Terminal Fatty Acid Substitution Increases the
Leishmanicidal Activity of CA(1-7)M(2-9), a Cecropin-Melittin
Hybrid Peptide

-7 lysine residue led to a drastic decrease in
leishmanicidal activity, whereas acylation at lysine 1, in either the
or the
NH2 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.
*
Corresponding author. Mailing address: Centro de
Investigaciones Biológicas, Velázquez 144, E-28006, Madrid,
Spain. Phone: 34 915 611 800, ext. 4234. Fax: 34 915 627 518. E-mail:
luis_rivas{at}cib.csic.es.
Present address: Roche Discovery, Welwyn, Hertfordshire, United Kingdom.
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