Total Synthesis of Homogeneous Variants of Hirudin P6: A Post‐Translationally Modified Anti‐Thrombotic Leech‐Derived Protein | Zendy

Hsieh Yves S. Y. | Zendy; Wijeyewickrema Lakshmi C. | Zendy; Wilkinson Brendan L. | Zendy; Pike Robert N. | Zendy; Payne Richard J. | Zendy

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Total Synthesis of Homogeneous Variants of Hirudin P6: A Post‐Translationally Modified Anti‐Thrombotic Leech‐Derived Protein

Author(s) -

Hsieh Yves S. Y.,

Wijeyewickrema Lakshmi C.,

Wilkinson Brendan L.,

Pike Robert N.,

Payne Richard J.

Publication year - 2014

Publication title -

angewandte chemie international edition

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.831

H-Index - 550

eISSN - 1521-3773

pISSN - 1433-7851

DOI - 10.1002/anie.201310777

Subject(s) - hirudin , glycosylation , sulfation , chemistry , leech , homogeneous , thrombin , glycoprotein , biochemistry , tyrosine , biology , platelet , immunology , computer science , physics , world wide web , thermodynamics

Hirudin P6 is a leech‐derived anti‐thrombotic protein which possesses two post‐translational modifications, O ‐glycosylation and tyrosine sulfation. In this study we report the ligation‐based synthesis of a library of hirudin P6 proteins possessing homogeneous glycosylation and sulfation modifications. The nature of the modifications incorporated was shown to have a drastic effect on inhibition against both the fibrinogenolytic and amidolytic activities of thrombin and thus highlights a potential means for attenuating the biological activity of the protein.

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