Total Synthesis of Homogeneous Variants of Hirudin P6: A Post‐Translationally Modified Anti‐Thrombotic Leech‐Derived Protein |
| |
| Authors: | Yves S. Y. Hsieh Dr. Lakshmi C. Wijeyewickrema Dr. Brendan L. Wilkinson Prof. Robert N. Pike Prof. Richard J. Payne |
| |
| Affiliation: | 1. School of Chemistry, The University of Sydney, Sydney, NSW 2006 (Australia) http://sydney.edu.au/science/chemistry/～payne/index;2. Department of Biochemistry and Molecular Biology, Monash University, VIC 3800 (Australia) |
| |
| 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. |
| |
| Keywords: | glycoprotein glycosylation ligation sulfation sulfoprotein |
|
