Synthesis and Analysis of Biochemical and Pharmaceutical Properties of Polysialylated Recombinant Streptokinase Enzyme.

Authors

Hamid Shahbazmohammadi, Eskandar Omidinia

Published in

Biotechnology and applied biochemistry. Aug 31, 2026. Epub Aug 31, 2026.

Abstract

Streptokinase (SK) is an enzyme drug and is used in medicine for dissolving clots in conditions such as heart attacks, lung artery emboli, vein thrombosis, and occlusions of arteries. Despite the impressive use of SK, its immunogenicity and short half-life are major challenges that limit its efficacy in clinical settings. In this communication, we studied the polysialylation of SK with the aim of improving the pharmacokinetics of this thrombolytic drug. Recombinant SK was covalently conjugated to polysialic acid (PSA; also referred to as colominic acid [CA]) via reductive amination. Native and polysialylated variants were compared in terms of structural properties, enzyme kinetics, stability, immunization, and biological half-life. The best molecular weight of PSA, optimum molar ratio, incubation time, and temperature for the conjugation reaction were determined to be 10.0 kDa, 200:1, 24 h, and 25°C, respectively. The exact molecular weight of SK-10.0 kDa PSA was determined to be 56.5 kDa by MALDI-TOF mass spectrometry, which matches the calculated value by SDS-PAGE. The intrinsic fluorescence intensity of polysialylated SK increased compared to the native version, meaning that the stability of SK was increased by immobilization on the PSA polymer. K_m of polysialylated SK was slightly higher than that of native SK, which showed that the attached PSA molecules to the enzyme did not significantly reduce the substrate specificity. Polysialylated SK elicited nearly 63.0% lower antibody production compared to the native variant. Native and polysialylated SKs exhibited plasma half-lives of 0.5 and 2.21 h, respectively, implying that the modified variant has a 4.42-fold longer residence time in the body. Briefly, comparative studies with native and PSA-conjugated enzymes show that polysialylation can be useful in enhancing the therapeutic efficacy of SK. It is worth emphasizing that this is the first report describing the use of polysialylation technology to improve the pharmaceutical properties of SK.

PMID:
42675018
Bibliographic data and abstract were imported from PubMed on 01 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.