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Myotoxic phospholipases A(2) isolated from Bothrops brazili snake venom and synthetic peptides derived from their C-terminal region: cytotoxic effect on microorganism and tumor cells.

Abstract：

:This paper reports the purification and biochemical/pharmacological characterization of two myotoxic phospholipases A(2) (PLA(2)s) from Bothrops brazili venom, a native snake from Brazil. Both myotoxins (MTX-I and II) were purified by a single chromatographic step on a CM-Sepharose ion-exchange column up to a high purity level, showing M(r) approximately 14,000 for the monomer and 28,000Da for the dimer. The N-terminal and internal peptide amino acid sequences showed similarity with other myotoxic PLA(2)s from snake venoms, MTX-I belonging to Asp49 PLA(2) class, enzymatically active, and MTX-II to Lys49 PLA(2)s, catalytically inactive. Treatment of MTX-I with BPB and EDTA reduced drastically its PLA(2) and anticoagulant activities, corroborating the importance of residue His48 and Ca(2+) ions for the enzymatic catalysis. Both PLA(2)s induced myotoxic activity and dose-time dependent edema similar to other isolated snake venom toxins from Bothrops and Crotalus genus. The results also demonstrated that MTXs and cationic synthetic peptides derived from their 115-129 C-terminal region displayed cytotoxic activity on human T-cell leukemia (JURKAT) lines and microbicidal effects against Escherichia coli, Candida albicans and Leishmania sp. Thus, these PLA(2) proteins and C-terminal synthetic peptides present multifunctional properties that might be of interest in the development of therapeutic strategies against parasites, bacteria and cancer.

journal_name

Peptides

journal_title

Peptides

authors

Costa TR,Menaldo DL,Oliveira CZ,Santos-Filho NA,Teixeira SS,Nomizo A,Fuly AL,Monteiro MC,de Souza BM,Palma MS,Stábeli RG,Sampaio SV,Soares AM

doi

10.1016/j.peptides.2008.05.021

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

1645-56

issue

10

eissn

0196-9781

issn

1873-5169

pii

S0196-9781(08)00244-1

journal_volume

29

pub_type

杂志文章

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