Samuel J. Danishefsky, Sloan-Kettering Institute for Cancer Research, New York, USA, and colleagues accomplished the first total synthesis of erythropoietin (EPO) wild type polypeptide (1–166), glycosidated at the three wild–type N-linked sites and the one O-linked site. The erythropoietic activity of the synthetic folded protein was demonstrated by the reseachers.
EPO is a glycoprotein hormone that stimulates the production of red blood cells by stem cells in bone marrow. Produced mainly by the kidneys, it is released in response to decreased levels of oxygen in body tissue.
Being able to chemically synthesize even a complex glycoprotein in foldable, biologically functional, form, new understandings as to why nature glycosidates many proteins might be possible. Such understandings might help improve therapeutic applications.
- At Last: Erythropoietin as a Single Glycoform,
P. Wang, S. Dong, J. A. Brailsford, K. Iyer, S. D. Townsend, Q. Zhang, R. C. Hendrickson, J. Shieh, M. A. S. Moore, S. J. Danishefsky,
Angew. Chem. Int. Ed. 2012.
DOI: 10.1002/anie.201206090
