Toward conditional control of Smac mimetic activity by RNA-templated reduction of azidopeptides on PNA or 2′-OMe-RNA,Biopolymers

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Toward conditional control of Smac mimetic activity by RNA-templated reduction of azidopeptides on PNA or 2′-OMe-RNA
Biopolymers ( IF 3.2 ) Pub Date : 2021-07-19 , DOI: 10.1002/bip.23466
Yannic Altrichter ₁ , Justus Schöller ₁ , Oliver Seitz ₁

Affiliation

Oligonucleotide templated reactions can be used to control the activity of functional molecules based on the presence of a specific trigger sequence. We report an RNA-controlled reaction system to conditionally restore the N-terminal amino group and thus binding affinity of azide-modified Smac mimetic compounds (SMCs) for their target protein X-linked Inhibitor of Apoptosis Protein (XIAP). Two templated reactions were compared: Staudinger reduction with phosphines and a photocatalytic reaction with Ru(bpy)₂(mcbpy). The latter proved faster and more efficient, especially for the activation of a bivalent SMC, which requires two consecutive reduction steps. The templated reaction proceeds with turnover when 2′-OMe-RNA probes are used, but is significantly more efficient with PNA, catalyzing a reaction in the presence of low, substoichiometric amounts (1%-3%, 10 nM) of target RNA.

中文翻译：

通过 RNA 模板减少 PNA 或 2'-OMe-RNA 上的叠氮肽对 Smac 模拟活性的条件控制

基于特定触发序列的存在，寡核苷酸模板化反应可用于控制功能分子的活性。我们报告了一种 RNA 控制的反应系统，可以有条件地恢复 N 端氨基，从而恢复叠氮修饰的 Smac 模拟化合物 (SMC) 对其靶蛋白 X 连锁凋亡蛋白抑制剂 (XIAP) 的结合亲和力。比较了两种模板化反应：用膦进行施陶丁格还原反应和用 Ru(bpy) _{2进行的光催化反应}(mcbpy)。后者被证明更快、更有效，特别是对于需要两个连续还原步骤的二价 SMC 的激活。当使用 2'-OMe-RNA 探针时，模板化反应随着周转而进行，但使用 PNA 时效率显着提高，在低、亚化学计量量 (1%-3%, 10 nM) 的靶 RNA 存在下催化反应。

更新日期：2021-07-19

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