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

Autor: Girish Sahni, Pooja Sawhney, Keya Katare
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Plasmin
Physiology
Glycobiology
lcsh:Medicine
Pharmacology
Pharmacokinetic Analysis
Biochemistry
Polyethylene Glycols
Mice
Elimination Half-Life Calculation
Immune Physiology
Medicine and Health Sciences
Medicine
Streptokinase
Post-Translational Modification
Amino Acids
lcsh:Science
Multidisciplinary
Immune System Proteins
biology
Organic Compounds
Hematology
Antibodies
Bacterial
Enzymes
Body Fluids
Chemistry
Blood
Physical Sciences
Anatomy
medicine.drug
Research Article
Plasmins
Immunology
Fibrin
Blood Plasma
03 medical and health sciences
Fibrinolytic Agents
In vivo
Thrombolytic Agent
Animals
Sulfur Containing Amino Acids
Cysteine
Antigens
Glycoproteins
business.industry
Activator (genetics)
Organic Chemistry
lcsh:R
Chemical Compounds
Streptococcus
Biology and Life Sciences
Proteins
Fibrinogen
Pegylation
030104 developmental biology
Pharmacologic Analysis
Amino Acid Substitution
biology.protein
PEGylation
Enzymology
lcsh:Q
business
Fibrinolytic agent
Zdroj: PLoS ONE, Vol 11, Iss 5, p e0155831 (2016)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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