title: Total synthesis of homogeneous variants of hirudin P6: a post-translationally modified anti-thrombotic leech-derived protein.
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.
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, NSW 2006 (Australia) http://sydney.edu.au/science/chemistry/∼payne/index.
authors.forename: Yves S Y
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Lakshmi C
authors.initials: LC
authors.lastname: Wijeyewickrema
authors.forename: Brendan L
authors.initials: BL
authors.lastname: Wilkinson
authors.forename: Robert N
authors.initials: RN
authors.lastname: Pike
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Payne
mesh_terms: D000818:Animals; D006023:Glycoproteins; D006031:Glycosylation; D006629:Hirudins / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011499:Protein Processing, Post-Translational / Q000502:physiology*
chemical_list: D006023:Glycoproteins; D006629:Hirudins
keywords: glycoprotein; glycosylation; ligation; sulfation; sulfoprotein