Department of Biology and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Org Lett. 2022 Mar 25;24(11):2170-2174. doi: 10.1021/acs.orglett.2c00462. Epub 2022 Mar 10.
Nucleoside diphosphate sugar (NDP-sugar) substrates provide the inspiration for nucleoside analogue inhibitor scaffolds. By employing solid-phase synthesis, we provide a method to access a library of peptidouridine inhibitors with both minimal compound handling and purification steps. Specifically, this strategy is exemplified by generating uridine diphosphate sugar (UDP-sugar) mimics, which allow for compound elaboration by altering the dipeptide composition, the N-terminal linkage, and a pendant aryl group. To exemplify the versatility, 41 unique nucleoside analogues are presented.
核苷二磷酸糖(NDP-sugar)底物为核苷类似物抑制剂支架提供了灵感。通过采用固相合成,我们提供了一种方法来获得具有最小化合物处理和纯化步骤的肽尿嘧啶抑制剂文库。具体来说,通过改变二肽组成、N 末端连接和芳基侧链,生成尿苷二磷酸糖(UDP-sugar)类似物来举例说明这种策略。为了说明其多功能性,展示了 41 种独特的核苷类似物。