Total Synthesis of Homogeneous Variants of Hirudin P6: A Post‐Translationally Modified Anti‐Thrombotic Leech‐Derived Protein
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Open Access
Type
ArticleAuthor/s
Hsieh, Yves S. Y.Wijeyewickrema, Lakshmi C.
Wilkinson, Brendan L.
Pike, Robert N.
Payne, Richard J.
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.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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Date
2014-03-11Publisher
WileyFunding information
ARC FT130100150Licence
OtherFaculty/School
Faculty of ScienceShare