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

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title PEGylation of Truncated Streptokinase Leads to Formulation of a Useful Drug with Ameliorated Attributes.
 
Creator Sawhney, Pooja
Katare, Keya
Sahni, Girish
 
Subject QR Microbiology
 
Description 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.
 
Publisher Public Library of Science
 
Date 2016
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1902/1/76.pdf
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
 
Relation http://dx.plos.org/10.1371/journal.pone.0155831
http://crdd.osdd.net/open/1902/