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首页> 外文期刊>Chemistry: A European journal >Synthesis and stereochemical assignment of DNA spore photoproduct analogues
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Synthesis and stereochemical assignment of DNA spore photoproduct analogues

机译：DNA孢子光产物类似物的合成和立体化学分配

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Investigation of the DNA repair process per-formed by the spore photoproduct (SP) lyase repair enzyme is strongly hampered by the lack of defined substrates needed for detailed enzymatic studies. The problem is particularly severe because the repair enzyme belongs to the class of strongly oxygen-sensitive radical (S)-adenosyl-methionine (SAM) enzymes, which are notoriously difficult to handle. We report the synthesis of the spore photoproduct analogues 1a and 1b, which have open backbones and are diastereoisomers. In order to solve the problem of stereochemical assignment, two further derivatives 2a and 2b with closed backbones were prepared. The key step of the synthesis of 2a/b is a metathesis-based macrocyclization that strongly increases the conformational rigidity of the synthetic spore photoproduct derivatives. NOESY experiments of the cyclic isomers furnished a clear cross-peak pattern that allowed the unequivocal assignment of the stereochemistry. The results were transferred to the data for isomers la and 1b, which were subsequently used for enzymatic-repair studies. These studies were performed with the novel spore photoproduct lyase repair enzyme from Geobacillus stearothermophilus. The studies showed an accordance with a recent investigation performed by us with the spore photoproduct lyase from Bacillus subtilis,([1]) in that only the S isomer la is recognized and repaired. The ability to prepare a defined functioning substrate now paves the way for detailed enzymatic studies of the SP-lyase lesion recognition and repair process.
机译：缺乏详细酶学研究所需的明确底物，严重阻碍了孢子光产物（SP）裂解酶修复酶对DNA修复过程的研究。这个问题特别严重，因为修复酶属于强氧敏感性自由基（S）-腺苷甲硫氨酸（SAM）酶，众所周知，这种酶很难处理。我们报告了孢子光产物类似物1a和1b的合成，它们具有开放的骨架和非对映异构体。为了解决立体化学分配的问题，制备了另外两个具有封闭主链的衍生物2a和2b。合成2a / b的关键步骤是基于易位的大环化，可大大提高合成孢子光产物衍生物的构象刚度。环状异构体的NOESY实验提供了清晰的交叉峰图案，可以明确地确定立体化学。将结果转移到异构体1a和1b的数据中，随后将其用于酶修复研究。这些研究是用来自嗜热脂肪地芽孢杆菌的新型孢子光产物裂解酶修复酶进行的。研究表明，根据我们最近对枯草芽孢杆菌的孢子光产物裂解酶的研究结果，[1]仅识别和修复了S异构体la。现在，制备确定的功能性底物的能力为SP裂解酶损伤识别和修复过程的详细酶学研究铺平了道路。

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