PEGylation effect on StAP3 cytotoxic activity

F.F. MUÑOZ; P.C. CARACCIOLO; G.R. DALEO; G.A. ABRAHAM; M.G: GUEVARA

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología, SAIB; 2012

Sociedad Argentina de Investigaci¨®n Bioqu¨ªmica y Biolog¨ªa, SAIB

PEGylation (i.e. the covalent link of PEG strands) is a technique used to improve pharmaceutical properties of bioactive proteins and peptides, mainly improving the serum half-life, and reducing the immunogenicity and the enzymatic degradation. We have previously reported the purification and characterization of potato aspartic proteases (StAPs) with antimicrobial/antitumor activity. Selective cytotoxic activity of StAPs suggests that, these proteins could be used to develop alternative drugs to contribute to resolve the increasing resistance of pathogenic bacteria to conventional antibiotics. In this work we have analyzed the ability of PEGylation to improve StAPs antimicrobial activity. PEGylation of StAP3 was performed at pH 6 and 8, obtaining higher performance at pH 8. Results obtained show that, PEG-conjugated StAP3 exerts cytotoxic activity towards Fusarium solani. IC50 estimated to PEG-conjugated StAP3 was 9 g/ml. Like free StAP3, PEG-conjugated StAP3 is able to interact and to permeabilize spores and hyphae plasma cell membranes in a dose-dependent manner. The results obtained here indicate that PEGylation increases the cytotoxic activity of StAP3.