Backbone-Anchoring, Solid-Phase Synthesis Strategy To Access a Library of Peptidouridine-Containing Small Molecules.

Backbone-Anchoring, Solid-Phase Synthesis Strategy To Access a Library of Peptidouridine-Containing Small Molecules.
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DOI:
10.1021/acs.orglett.2c00462
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发表时间:
2022-03-25
期刊:
影响因子:
5.2
通讯作者:
Imperiali, Barbara
Imperiali, Barbara
中科院分区:
化学1区
文献类型:
--
作者:
Arbour, Christine A.;Imperiali, Barbara

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核苷二磷酸糖(NDP-糖)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访问库的肽尿苷抑制剂与最小的化合物处理和纯化步骤。具体地,该策略通过产生尿苷二磷酸糖(UDP-糖)模拟物来举例说明,其允许通过改变二肽组成、N-末端连接和侧芳基来进行化合物精制。为了证明多功能性,提出了41种独特的核苷类似物。
Nucleoside diphosphate sugar (NDP-sugar) substrates provide the inspiration for nucleoside analog 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 allows compound elaboration by altering the dipeptide composition, the N-terminal linkage, and a pendant aryl group. To exemplify the versatility 41 unique nucleoside analogs are presented.
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