Enhanced epimerization of glycosylated amino acids during solid-phase peptide synthesis.
Enhanced epimerization of glycosylated amino acids during solid-phase peptide synthesis.
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DOI：
10.1021/ja212188r
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发表时间：
2012-04-11
影响因子：
15
通讯作者：
Gildersleeve, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Zhang, Yalong;Muthana, Saddam M.;Farnsworth, David;Ludek, Olaf;Adams, Kristie;Barchi, Joseph J., Jr.;Gildersleeve, Jeffrey C.
Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally-defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the alpha position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to non-glycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens.
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影响因子：
7.3
作者：
Kaczmarek P;Keay SK;Tocci GM;Koch KR;Zhang CO;Barchi JJ Jr;Grkovic D;Guo L;Michejda CJ
通讯作者：
Michejda CJ
DOI：
10.1039/c39940002383
发表时间：
1994-10-21
影响因子：
--
作者：
ARSEQUELL, G;KRIPPNER, L;WONG, SYC
通讯作者：
WONG, SYC
影响因子：
2.9
作者：
Hojo, Hironobu;Nakahara, Yoshiaki
通讯作者：
Nakahara, Yoshiaki
影响因子：
15
作者：
Hojo, H;Matsumoto, Y;Nakahara, Y
通讯作者：
Nakahara, Y
影响因子：
4.4
作者：
Kracun, Stjepan K.;Clo, Emiliano;Clausen, Henrik;Levery, Steven B.;Jensen, Knud J.;Blixt, Ola
通讯作者：
Blixt, Ola