Diazaborine-Mediated Bicyclization of Native Peptides with Inducible Reversibility.
Diazaborine-Mediated Bicyclization of Native Peptides with Inducible Reversibility.
复制标题
二氮杂硼啉介导的具有诱导可逆性的天然肽双环化。
DOI：
10.1021/acs.orglett.3c01496
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发表时间：
2023
期刊：
影响因子：
5.2
通讯作者：
Gao,Jianmin
中科院分区：
文献类型：
--
作者：
Reja,RahiM;Chau,Brittney;Gao,Jianmin
多环肽是基于肽的药物发现的有吸引力的候选者。虽然开发了各种方法用于肽环化，但很少允许天然肽的多环化。本文中，我们报告了一种新的交联剂DCA-RMR 1，其通过N-末端Cys-Cys交联使天然肽易于双环化。双环化是快速的，提供定量转化，并容许各种侧链官能团。重要的是，所得的二氮杂硼杂环戊烯键虽然在中性pH下稳定，但在轻度酸化后可以容易地逆转，得到pH响应性肽。
Multicyclic peptides are appealing candidates for peptide-based drug discovery. While various methods are developed for peptide cyclization, few allow multicyclization of native peptides. Herein we report a novel cross-linker DCA-RMR1, which elicits facile bicyclization of native peptides via N-terminus Cys-Cys cross-linking. The bicyclization is fast, affords quantitative conversion, and tolerates various side chain functionalities. Importantly, the resulting diazaborine linkage, while stable at a neutral pH, can readily reverse upon mild acidification to give pH-responsive peptides.