School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
Org Biomol Chem. 2022 Aug 17;20(32):6324-6328. doi: 10.1039/d2ob01011a.
4-Substituted prolines, especially 4-fluoroprolines, have been widely used in protein engineering and design. Here, we report a robust and stereoselective approach for the synthesis of (2,4)-methylproline starting from (2)-pyroglutamic acid. Incorporation studies with both (2,4)- and (2,4)-methylproline into the Trx1P variant of the model protein thioredoxin of show that the stereochemistry of the 4-methyl group might be a key determinator for successful incorporation during ribosomal synthesis of this protein.
4-取代脯氨酸，特别是 4-氟脯氨酸，已被广泛用于蛋白质工程和设计。在这里，我们报告了一种从（2）-焦谷氨酸酸起始合成（2,4）-甲基脯氨酸的稳健和立体选择性方法。将（2,4）-和（2,4）-甲基脯氨酸掺入模型蛋白硫氧还蛋白的 Trx1P 变体中进行的掺入研究表明，4-甲基基团的立体化学可能是核糖体合成该蛋白时成功掺入的关键决定因素。
