Selective desulfurization significantly expands sequence variety of 3'-peptidyl-tRNA mimics obtained by native chemical ligation.
Selective desulfurization significantly expands sequence variety of 3'-peptidyl-tRNA mimics obtained by native chemical ligation.
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DOI：
10.1002/cbic.201200368
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发表时间：
2012-08-13
期刊：
影响因子：
3.2
通讯作者：
Micura, Ronald
中科院分区：
文献类型：
--
作者：
Geiermann, Anna-Skrollan;Micura, Ronald
模拟酰化 tRNA 末端的 RNA-肽缀合物对于核糖体延伸循环的结构和功能研究来说是有价值的化合物，特别是如果它们在 RNA 和肽部分之间含有抗水解连接的话。 [1]嘌呤霉素 ((S)-3’-((2-氨基-3-(4-甲氧基苯基)-1-氧代丙基)氨基)-3’-脱氧-N,N-二甲基腺苷) 的高度还原形式具有酰胺连接而不是酯连接，代表了这种稳定的缀合物。 [2]例如，这种模拟物被定位为核糖体肽基转移酶中心 (PTC) P 位的底物，以捕获肽键形成过程中的快照，并通过 X 射线晶体学进行分析。 [3]最近的一个例子利用短的、稳定的 3'-氨酰基-RNA 缀合物来探索新生肽链如何触发核糖体停滞，并通过各种生化方法进行分析。 [4]合成此类生物缀合物的直接实验方法预计将刺激核糖体延伸循环中不同状态的进一步研究和功能表征。[5]3'-氨基酰基-和3'-肽基-RNA的总合成对有机化学家来说是巨大的挑战；[2c, d]因此，我们研究的中心重点是这些衍生物的从头合成。[6]我们最近阐述了一种收敛策略，涉及 3'-半胱氨基-3'-脱氧-RNA 和肽硫酯的天然化学连接 (NCL)。 [7] NCL 最初是为了在温和条件下连接未受保护的肽片段而开发的，这种方法最终成为化学蛋白质合成的重大进展。 [8]我们的工作表明，NCL 也可以在 RNA 环境中有效发挥作用 [7]，因此可以作为 RNA 生物共轭领域进一步研究的起点。
RNA–peptide conjugates that mimic acylated tRNA termini are valuable compounds for structural and functional studies of the ribosomal elongation cycle, particularly if they contain a hydrolysis-resistant linkage between the RNA and the peptide moiety.[1] In a very reduced form, puromycin ((S)-3’-((2-amino-3-(4-methoxyphenyl)-1-oxopropyl) amino)-3’-desoxy-N, N-dimethyladenosine), which possesses an amide instead of an ester junction, represents such a stable conjugate.[2] This mimic, for example, was positioned as a substrate in the P-site of the ribosomal peptidyl transferase center (PTC) to capture snapshots along the route to peptide bond formation, as analyzed by X-ray crystallography.[3] A more recent example made use of short, stable, 3’-aminoacyl-RNA conjugates to explore how the nascent peptide chain triggers ribosomal stalling, as analyzed by a variety of biochemical methods.[4] Straightforward experimental approaches to synthesize this type of bioconjugate are expected to stimulate further investigations and functional characterization of the different states along the ribosomal elongation cycle.[5]The total syntheses of 3’-aminoacyl-and 3’-peptidyl-RNA represent substantive challenges for organic chemists;[2c, d] therefore, a central focus of our research is the de novo synthesis of these derivatives.[6] We have recently elaborated a convergent strategy that involves native chemical ligation (NCL) of 3’-cysteinylamino-3’-deoxy-RNA and peptide thioesters.[7] NCL was originally developed to link unprotected peptide fragments under mild conditions, and this approach eventually emerged as a major advance in chemical protein synthesis.[8] Our work has shown that NCL can also work efficiently in the context of RNA [7] and therefore might serve as a launching point for further investigations in the field of RNA bioconjugation.
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影响因子：
15
作者：
Jacobs, Aaron C.;Resendiz, Marino J. E.;Greenberg, Marc M.
通讯作者：
Greenberg, Marc M.
影响因子：
16.6
作者：
Haase, Christian;Rohde, Heike;Seitz, Oliver
通讯作者：
Seitz, Oliver
影响因子：
56.9
作者：
DAWSON, PE;MUIR, TW;KENT, SBH
通讯作者：
KENT, SBH
影响因子：
64.8
作者：
Hiller, David A.;Singh, Vipender;Zhong, Minghong;Strobel, Scott A.
通讯作者：
Strobel, Scott A.
DOI：
10.1126/science.1202692
发表时间：
2011-05-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dunkle JA;Wang L;Feldman MB;Pulk A;Chen VB;Kapral GJ;Noeske J;Richardson JS;Blanchard SC;Cate JH
通讯作者：
Cate JH