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醛催化的α-氨基酸与同位素标记CO2的羧酸盐交换
作者:小柯机器人 发布时间:2022/11/9 15:01:21

加拿大阿尔伯塔大学Lundgren Rylan J.团队报道了醛催化的α-氨基酸与同位素标记CO2的羧酸盐交换。相关研究成果发表在2022年11月7日出版的国际知名学术期刊《自然—化学》。

小分子的同位素标记对于药物开发和理解生化过程是不可或缺的。现有方法包括在合成的早期阶段加入标记,碳标记的α-氨基酸的制备仍然困难且耗时。这解释了C-标记产品的高成本和稀缺性,并在11C应用中提出了一个重大挑战(11C t1/2=20分钟)。

该文报道了醛催化天然α-氨基酸与*CO2(*=14,13,11)的同位素羧酸交换。蛋白质生成的α-氨基酸和许多含有不同官能团的非天然变体都要进行标记。反应可能通过亚胺羧酸盐中间体捕获CO2来进行,以生成易于单脱羧的亚氨基丙烯酸酯。回火催化剂的亲电性是防止不可逆醛消耗的关键。亚胺羧酸盐中间体的预生成能够在[11C]CO2存在下,对α-氨基酸进行快速和晚期的11C放射性标记。

附:英文原文

Title: Aldehyde-catalysed carboxylate exchange in α-amino acids with isotopically labelled CO2

Author: Bsharat, Odey, Doyle, Michael G. J., Munch, Maxime, Mair, Braeden A., Cooze, Christopher J. C., Derdau, Volker, Bauer, Armin, Kong, Duanyang, Rotstein, Benjamin H., Lundgren, Rylan J.

Issue&Volume: 2022-11-07

Abstract: The isotopic labelling of small molecules is integral to drug development and for understanding biochemical processes. The preparation of carbon-labelled α-amino acids remains difficult and time consuming, with established methods involving label incorporation at an early stage of synthesis. This explains the high cost and scarcity of C-labelled products and presents a major challenge in 11C applications (11C t1/2=20min). Here we report that aldehydes catalyse the isotopic carboxylate exchange of native α-amino acids with *CO2 (*=14, 13, 11). Proteinogenic α-amino acids and many non-natural variants containing diverse functional groups undergo labelling. The reaction probably proceeds via the trapping of *CO2 by imine-carboxylate intermediates to generate iminomalonates that are prone to monodecarboxylation. Tempering catalyst electrophilicity was key to preventing irreversible aldehyde consumption. The pre-generation of the imine carboxylate intermediate allows for the rapid and late-stage 11C-radiolabelling of α-amino acids in the presence of [11C]CO2.

DOI: 10.1038/s41557-022-01074-0

Source: https://www.nature.com/articles/s41557-022-01074-0

期刊信息

Nature Chemistry:《自然—化学》,创刊于2009年。隶属于施普林格·自然出版集团,最新IF:21.687
官方网址:https://www.nature.com/nchem/
投稿链接:https://mts-nchem.nature.com/cgi-bin/main.plex