吡咯并[1,2-a]苯并咪唑对DNA磷酸骨架的烷基化和切割证据：能够引起碱基对特异性磷酸二酯键水解的小分子。
Evidence for DNA phosphate backbone alkylation and cleavage by pyrrolo[1,2-a]benzimidazoles: small molecules capable of causing base-pair-specific phosphodiester bond hydrolysis.
作者信息
Schulz W G, Nieman R A, Skibo E B
机构信息
Department of Chemistry and Biochemistry, Arizona State University, Tempe 85287-1604, USA.
出版信息
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11854-8. doi: 10.1073/pnas.92.25.11854.
Abstract
This report presents evidence that a reduced pyrrolo[1,2-a]benzimidazole (PBI) cleaves DNA as a result of phosphate alkylation followed by hydrolysis of the resulting phosphate triester. The base-pair specificity of the phosphate alkylation results from Hoogsteen-type hydrogen bonding of the reduced PBI in the major groove at only A.T and G.C base pairs. Alkylated phosphates were detected by 31P NMR and the cleavage products were detected by 1H NMR and HPLC. Evidence is also presented that a reduced PBI interacts with DNA in the major groove rather than in the minor groove or by intercalation.
摘要
本报告提供的证据表明，还原态的吡咯并[1,2-a]苯并咪唑（PBI）由于磷酸烷基化，随后生成的磷酸三酯水解，从而切割DNA。磷酸烷基化的碱基对特异性源于还原态PBI仅在A.T和G.C碱基对的大沟中通过Hoogsteen型氢键作用。通过31P NMR检测烷基化的磷酸盐，通过1H NMR和HPLC检测切割产物。还提供了证据表明，还原态PBI与DNA在大沟中相互作用，而非在小沟中或通过嵌入作用。
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