Erythropoietin derived by chemical synthesis Journal Article
| Authors: | Wang, P.; Dong, S.; Shieh, J.H.; Peguero, E.; Hendrickson, R.; Moore, M. A. S.; Danishefsky, S. J. |
| Article Title: | Erythropoietin derived by chemical synthesis |
| Abstract: | Erythropoietin is a signaling glycoprotein that controls the fundamental process of erythropoiesis, orchestrating the production and maintenance of red blood cells. As administrated clinically, erythropoietin has a polypeptide backbone with complex dishomogeneity in its carbohydrate domains. Here we describe the total synthesis of homogeneous erythropoietin with consensus carbohydrate domains incorporated at all of the native glycosylation sites. The oligosaccharide sectors were built by total synthesis and attached stereospecifically to peptidyl fragments of the wild-type primary sequence, themselves obtained by solid-phase peptide synthesis. The glycopeptidyl constructs were joined by chemical ligation, followed by metal-free dethiylation, and subsequently folded. This homogeneous erythropoietin glycosylated at the three wild-type aspartates with N-linked high-mannose sialic acid -containing oligosaccharides and O-linked glycophorin exhibits Procrit-level in vivo activity in mice. |
| Journal Title: | Science |
| Volume: | 342 |
| Issue: | 6164 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2013-12-13 |
| Start Page: | 1357 |
| End Page: | 1360 |
| Language: | English |
| DOI: | 10.1126/science.1245095 |
| PROVIDER: | scopus |
| PUBMED: | 24337294 |
| PMCID: | PMC4080428 |
| DOI/URL: | |
| Notes: | Cited By (since 1996):1 -- Export Date: 2 January 2014 -- CODEN: SCIEA -- Source: Scopus |
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19Wang -
539Danishefsky -
76
Shieh -
8
Dong -
549Moore -
83Hendrickson -
11Peguero
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