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Total Synthesis of Homogeneous Variants of Hirudin P6: A Post-Translationally Modified Anti-Thrombotic Leech-Derived Protein |
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Wijeyewickrema, Lakshmi C |
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Wiley-VCH Verlag GmbH & Co KGaA |
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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. |
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Angewandte Chemie (International Edition), 53(15), p. 3947-3951 |
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