Toward homogeneous erythropoietin: Fine tuning of the C-terminal acyl donor in the chemical synthesis of the Cys(29)-Gly(77) glycopeptide domain Journal Article
| Authors: | Yuan, Y.; Chen, J.; Wan, Q.; Tan, Z.; Chen, G.; Kan, C.; Danishefsky, S. J. |
| Article Title: | Toward homogeneous erythropoietin: Fine tuning of the C-terminal acyl donor in the chemical synthesis of the Cys(29)-Gly(77) glycopeptide domain |
| Abstract: | Described herein is the chemical synthesis of the Cys(29)-Gly (77) glycopeptide domain (22) of erythropoietin. Our initial ligation strategy targeted a C → N termini condensation between glycopeptide 3 and peptide 4. However, the reaction was hindered by the "unattainable" reactivity, mismatched polarity, and severe aggregation of the (glyco)peptide substrates. In contrast, by tuning the C-terminal acyl donor and using smaller peptide fragments, the Cys(29)-Gly(77) glycopeptide domain of erythropoietin was prepared through unconventional N → C termini condensation reactions. The use of a p-cyanonitrophenyl ester and the development of a masked thiophenyl ester as acyl donors enabled us to promptly access glycopeptides bearing complex carbohydrates and offer potential synthetic applications beyond our current work. © 2009 American Chemical Society. |
| Keywords: | protein domain; erythropoietin; carboxy terminal sequence; amines; amino terminal sequence; protein synthesis; polymerization; peptide fragments; peptide fragment; protein structure, tertiary; esterification; chemical structure; polysaccharide; polysaccharides; protein tertiary structure; chemical reaction; synthesis; synthesis (chemical); carbohydrates; glycopeptide; glycopeptides; sulfur compounds; chemical synthesis; cysteine; carbohydrate; glycine; chemical procedures; peptide substrates; esters; acyl donors; complex carbohydrates; fine tuning; synthetic application; thiophenyl; condensation; condensation reactions; tuning; ester; phenylacetic acid derivative; thiophenyl acetate; acylation; phenylacetates |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 131 |
| Issue: | 15 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 2009-04-22 |
| Start Page: | 5432 |
| End Page: | 5437 |
| Language: | English |
| DOI: | 10.1021/ja808705v |
| PUBMED: | 20560636 |
| PROVIDER: | scopus |
| PMCID: | PMC2891568 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 12" - "Export Date: 30 November 2010" - "CODEN: JACSA" - "Source: Scopus" |
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