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首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Profiling base excision repair glycosylases with synthesized transition state analogs.
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Profiling base excision repair glycosylases with synthesized transition state analogs.

机译:用合成的过渡态类似物分析碱基切除修复糖基化酶。

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摘要

Two base excision repair glycosylase (BER) transition state (TS) mimics, (3R,4R)-1-benzyl (hydroxymethyl) pyrrolidin-3-ol (1NBn) and (3R,4R)-(hydroxymethyl) pyrrolidin-3-ol (1N), were synthesized using an improved method. Several BER glycosylases that repair oxidized DNA bases, bacterial formamidopyrimdine glycosylase (Fpg), human OG glycosylase (hOGG1) and human Nei-like glycosylase 1 (hNEIL1) exhibit exceptionally high affinity (K(d) approximately pM) with DNA duplexes containing the 1NBn and 1N nucleotide. Notably, comparison of the K(d) values of both TS mimics relative to an abasic analog (THF) in duplex contexts paired opposite C or A suggest that these DNA repair enzymes use distinctly different mechanisms for damaged base recognition and catalysis despite having overlapping substrate specificities.
机译:两个碱基切除修复糖基化酶(BER)过渡态(TS)模仿物,(3R,4R)-1-苄基(羟甲基)吡咯烷-3-醇(1NBn)和(3R,4R)-(羟甲基)吡咯烷-3-醇(1N),使用改进的方法合成。几种可修复氧化的DNA碱基的BER糖基化酶,细菌甲酰胺基嘧啶糖基化酶(Fpg),人OG糖基化酶(hOGG1)和人Nei样糖基化酶1(hNEIL1)与含有1NBn的DNA双链体具有极高的亲和力(K(d)约pM)。和1N核苷酸。值得注意的是,在与C或A配对的双工环境中,两种TS模拟物相对于无碱基类似物(THF)的K(d)值的比较表明,尽管底物重叠,但这些DNA修复酶使用明显不同的机制进行碱基识别和催化损伤特殊性。

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