Promising general solution to the problem of ligating peptides and glycopeptides Journal Article
| Authors: | Wang, P.; Danishefsky, S. J. |
| Article Title: | Promising general solution to the problem of ligating peptides and glycopeptides |
| Abstract: | Our global goal is that of synthesizing complex polypeptides and glycopeptides in homogeneous form. Chemistry-derived access to homogeneous biologics could well have useful consequences in the discovery of drugs and vaccines. The key finding in this study is that thio acids can become highly competent acyl donors following even trace levels of oxidative activation, thereby undergoing amide bond formation upon reaction with N-terminal peptides. Though our data set does not establish the specific mechanism of this reaction, a framework to account for the fact that minute levels of oxidation actuate amide bond formation with high turnover is offered. An apparently general coupling of thio acids (including complex peptide thio acids with N-termini of complex peptides) has thus been realized. These ligations are conducted with minimal α-epimerization in the C-terminal group and allow for the coupling of N-terminal and C-terminal glycopeptides en route to homogeneous glycoproteins. © 2010 American Chemical Society. |
| Keywords: | controlled study; carboxy terminal sequence; protein binding; peptide; amino acid sequence; molecular sequence data; amino terminal sequence; peptides; oxidation; triazoles; acids; glycopeptide; glycopeptides; peptide synthesis; surgical equipment; chemical bond; acyl donors; general solutions; thioacids; amides; amide; data sets; homogeneous forms; turnover time; n-terminals; amide bond formation; en-route; epimerization; general coupling; synthesizing complex; terminal groups; trace level; chemical bonds |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 132 |
| Issue: | 47 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 2010-12-01 |
| Start Page: | 17045 |
| End Page: | 17051 |
| Language: | English |
| DOI: | 10.1021/ja1084628 |
| PUBMED: | 21049949 |
| PROVIDER: | scopus |
| PMCID: | PMC3020898 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: JACSA" - "Source: Scopus" |
