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Type: Artigo de Periódico
Title: Scaffold Proteins Lack And Track As Potential Drug Targets In Kinetoplastid Parasites: Development Of Inhibitors
Author: Qvit
N; Schechtman
D; Pena
DA; Berti
DA; Soares
CO; Miao
QQ; Liang
LY; Baron
LA; Teh-Poot
C; Martinez-Vega
P; Ramirez-Sierra
MJ; Churchill
E; Cunningham
AD; Malkovskiy
AV; Federspiel
NA; Gozzo
FC; Torrecilhas
AC; Alves
MJM; Jardim
A; Momar
N; Dumonteil
E; Mochly-Rosen
Abstract: Parasitic diseases cause similar to 500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase) and TRACK (Trypanosoma receptor for activated C-kinase). We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase), may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology.
Subject: Chagas Disease
Scaffold Protein
Citation: International Journal For Parasitology: Drugs And Drug Resistance. ELSEVIER SCI LTD, n. 6, n. 1, p. 74 - 84.
Rights: aberto
Identifier DOI: 10.1016/j.ijpddr.2016.02.003
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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