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.
Hsieh, Y. SY., Wijeyewickrema, L. C., Wilkinson, B., Pike, R. N., & Payne, R. J. (2014). Total synthesis of homogeneous variants of hirudin P6: a post-translationally modified anti-thrombotic leech-derived protein. Angewandte Chemie - International Edition, 53(15), 3947 - 3951. https://doi.org/10.1002/anie.201310777