PEGylation of Truncated Streptokinase Leads to Formulation of a Useful Drug with Ameliorated Attributes.

Sawhney, Pooja and Katare, Keya and Sahni, Girish (2016) PEGylation of Truncated Streptokinase Leads to Formulation of a Useful Drug with Ameliorated Attributes. PloS one, 11 (5). e0155831. ISSN 1932-6203

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Abstract

Streptokinase (SK) remains a favored thrombolytic agent in the developing world as compared to the nearly 10-fold more expensive human tissue-plasminogen activator (tPA) for the dissolution of pathological fibrin clots in myocardial infarction. However, unlike the latter, SK induces systemic activation of plasmin which results in a greater risk of hemorrhage. Being of bacterial origin, it elicits generation of unwanted antibody and has a relatively short half-life in vivo that needs to be addressed to make it more efficacious clinically. In order to address these lacunae, in the present study we have incorporated cysteine residues specifically at the N- and C-termini of partially truncated SK and these were then PEGylated successfully. Some of the obtained derivatives displayed enhanced plasmin resistance, longer half-life (upto several hours), improved fibrin clot-specificity and reduced immune-reactivity as compared to the native SK (nSK). This paves the way for devising next-generation SK-based thrombolytic agent/s that besides being fibrin clot-specific are endowed with an improved efficacy by virtue of an extended in vivo half-life.

Item Type:	Article
Additional Information:	Open Access
Uncontrolled Keywords:	Streptokinase
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	29 Sep 2016 06:44
Last Modified:	29 Sep 2016 06:44
URI:	http://crdd.osdd.net/open/id/eprint/1902

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