Enhanced leishmanicidal activity of cryptopeptide chimeras from the active N1 domain of bovine lactoferrin

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Tania Silva (Author) Other; Maria A Angeles Abengozar (Author) Other; Maria Fernandez Reyes (Author) Other; David Andreu (Author) Other; Kamran Nazmi (Author) Other; Jan G M Bolscher (Author) Other; Margarida Bastos (Author) FCUP; Luis Rivas (Author) Other

Journal

Title: Amino Acids

Vol. 43

Pages: 2265-2277

ISSN: 0939-4451

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 23 Citations

Scopus - 25 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-002-31Q

DOI: 10.1007/s00726-012-1304-0

Abstract (EN): Two antimicrobial cryptopeptides from the N1 domain of bovine lactoferrin, lactoferricin (LFcin17-30) and lactoferrampin (LFampin265-284), together with a hybrid version (LFchimera), were tested against the protozoan parasite Leishmania. All peptides were leishmanicidal against Leishmania donovani promastigotes, and LFchimera showed a significantly higher activity over its two composing moieties. Besides, it was the only peptide active on Leishmania pifanoi axenic amastigotes, already showing activity below 10 mu M. To investigate their leishmanicidal mechanism, promastigote membrane permeabilization was assessed by decrease of free ATP levels in living parasites, entrance of the vital dye SYTOX Green (MW = 600 Da) and confocal and transmission electron microscopy. The peptides induced plasma membrane permeabilization and bioenergetic collapse of the parasites. To further clarify the structural traits underlying the increased leishmanicidal activity of LFchimera, the activity of several analogues was assessed. Results revealed that the high activity of these hybrid peptides seems to be related to the order and sequence orientation of the two cryptopeptide moieties, rather than to their particular linkage through an additional lysine, as in the initial LFchimera. The incorporation of both antimicrobial cryptopeptide motifs into a single linear sequence facilitates chemical synthesis and should help in the potential clinical application of these optimized analogues.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13