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

Language(s) - English

Resource type - Journals

eISSN - 1521-3757

pISSN - 0044-8249

DOI - 10.1002/ange.201310777

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