Total synthesis of homogeneous variants of hirudin P6: a post-translationally modified anti-thrombotic leech-derived protein

Yves SY Hsieh, Lakshmi C Wijeyewickrema, Brendan Wilkinson, Robert N Pike, Richard James Payne

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24 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)3947 - 3951
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number15
Publication statusPublished - 2014

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