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Wiley, Angewandte Chemie, 15(126), p. 4028-4032, 2014

DOI: 10.1002/ange.201310777

Wiley, Angewandte Chemie International Edition, 15(53), p. 3947-3951, 2014

DOI: 10.1002/anie.201310777

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

Journal article published in 2014 by Yves S. Y. Hsieh ORCID, Lakshmi C. Wijeyewickrema, Brendan L. Wilkinson ORCID, Robert N. Pike, Richard J. Payne
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This paper is available in a repository.

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Abstract

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.