马来酰亚胺在双链DNA上的形式[4 + 2]环加成反应。
Formal [4 + 2] Cycloadditions of Maleimides on Duplex DNA.
作者信息
Basran Kaleena, Bujalska Anna, Karimi Ashkan, Luedtke Nathan W
机构信息
Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec H3A 0B8, Canada.
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
出版信息
Bioconjug Chem. 2023 Jun 21;34(6):977-982. doi: 10.1021/acs.bioconjchem.3c00090. Epub 2023 Jun 8.
Near-quantitative DNA bioconjugation and detailed mechanistic investigations of reactions involving 5-(vinyl)-2'-deoxyuridine (VdU) and maleimides are reported. According to accelerated reaction rates in solvents with increasing polarity and trends in product stereochemistry, VdU-maleimide reactions proceed via a formal [4 + 2] stepwise cycloaddition. In contrast, 5-(1,3-butadienyl)-2'-deoxyuridine (BDdU) reacts with maleimides in a concerted [4 + 2] Diels-Alder cycloaddition. VdU-maleimide reactions enable high-yielding bioconjugation of duplex DNA in vitro (>90%) as well as metabolic labeling experiments in cells.
报道了5-(乙烯基)-2'-脱氧尿苷(VdU)与马来酰亚胺反应的近定量DNA生物共轭及详细的机理研究。根据在极性增加的溶剂中反应速率加快以及产物立体化学趋势，VdU-马来酰亚胺反应通过形式上的[4 + 2]逐步环加成进行。相比之下，5-(1,3-丁二烯基)-2'-脱氧尿苷(BDdU)与马来酰亚胺通过协同的[4 + 2]狄尔斯-阿尔德环加成反应。VdU-马来酰亚胺反应能够在体外实现双链DNA的高产率生物共轭(>90%)以及细胞中的代谢标记实验。
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