Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 45110 Ioanina, Greece.
Amino Acids. 2013 May;44(5):1357-63. doi: 10.1007/s00726-013-1471-7. Epub 2013 Mar 5.
Alkylation of sensitive amino acids during synthesis of biologically important peptides is a common and well-documented problem in Fmoc-based strategy. Herein, we probed for the first time an unexpected S-alkylation of Cys-containing peptides that occur during the final TFA cleavage of peptides from the Wang solid support. Through a battery of approaches (NMR, UV and LC-MS) the formed by-product was assigned as the alkylation of the cysteine sulfydryl group by the p-hydroxyl benzyl group derived from the acidic Wang linker decomposition. Factors affecting this side reaction were monitored and a protocol that minimizes the presence of the by-product is reported.
在基于 Fmoc 的策略中，在合成具有生物重要性的肽时，敏感氨基酸的烷基化是一个常见且有充分文献记录的问题。在此，我们首次探测到在从 Wang 固相载体上切割肽时，含半胱氨酸的肽发生了意想不到的 S-烷基化。通过一系列方法（NMR、UV 和 LC-MS），确定形成的副产物是由酸性 Wang 连接物分解产生的对羟基苄基基团对半胱氨酸巯基的烷基化。监测了影响此副反应的因素，并报道了一种最小化副产物存在的方案。
