Rovira Alexander R, Fin Andrea, Tor Yitzhak
Department of Chemistry and Biochemistry, University of California, San Diego , La Jolla, California 92093-0358, United States.
J Am Chem Soc. 2015 Nov 25;137(46):14602-5. doi: 10.1021/jacs.5b10420. Epub 2015 Nov 16.
An evolved fluorescent ribonucleoside alphabet comprising isomorphic purine ((tz)A, (tz)G) and pyrimidine ((tz)U, (tz)C) analogues, all derived from isothiazolo[4,3-d]pyrimidine as a common heterocyclic core, is described. Structural and biochemical analyses illustrate that the nucleosides, particularly the C-nucleosidic purine analogues, are faithful isomorphic and isofunctional surrogates of their natural counterparts and show improved features when compared to an RNA alphabet derived from thieno[3,4-d]-pyrimidine. The restoration of the nitrogen in a position equivalent to the purines' N7 leads to "isofunctional" behavior, as illustrated by the ability of adenosine deaminase to deaminate (tz)A as effectively as adenosine, the native substrate.
本文描述了一种经过进化的荧光核糖核苷字母表，它包含同构嘌呤（(tz)A、(tz)G）和嘧啶（(tz)U、(tz)C）类似物，所有这些类似物均源自异噻唑并[4,3-d]嘧啶作为共同的杂环核心。结构和生化分析表明，这些核苷，特别是C-核苷嘌呤类似物，是其天然对应物的忠实同构和同功能替代物，并且与源自噻吩并[3,4-d]嘧啶的RNA字母表相比，具有改进的特性。在与嘌呤的N7等效位置上氮的恢复导致“同功能”行为，如腺苷脱氨酶将(tz)A脱氨的能力与天然底物腺苷一样有效所证明。
