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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.