Guanine specific DNA cleavage by photoirradiation of dibenzoyldiazomethane-oligonucleotide conjugates
Guanine specific DNA cleavage by photoirradiation of dibenzoyldiazomethane-oligonucleotide conjugates
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通过光照射二苯甲酰重氮甲烷-寡核苷酸缀合物进行鸟嘌呤特异性 DNA 切割
DOI：
10.1021/ja970598j
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发表时间：
1997
影响因子：
15
通讯作者：
I. Saito
中科院分区：
文献类型：
--
作者：
K. Nakatani;Junya Shirai;S. Sando;I. Saito
二苯甲酰基重氮甲烷（DBDM）在光照下通过Wolff重排反应生成高度亲电的苯甲酰基烯酮。具有氨烷基侧链的DBDM衍生物在光照射和随后的哌啶处理时诱导DNA选择性地在鸟嘌呤（G）残基处切割。为了设计能够特异性烷基化长DNA片段靶序列附近鸟嘌呤残基的光化学DNA切割剂，开发了一种新的试剂DBDM-OSu，其促进DBDM单元与各种DNA结合剂的连接。DBDM-寡核苷酸（ODN）缀合物5和6通过在碳酸氢钠存在下在乙腈水溶液中分别将5 ′-氨基己基8-mer [H2 N-（CH 2）6-d（ACGTCAGG）-3 ′]和15-mer [H2 N-（CH 2）6-d（ACGTCAGGTGGCACT）-3 ′]与DBDM-OSu偶联来获得。在具有互补序列的25-mer 5 ′-d（AGTGCCACCTGACGTCTG 18 CTCTCTC）-3 ′存在下，5和6的光辐射诱导两种寡聚体的交联。在鸟嘌呤残基上有明显的分裂带...
Photoirradiation of dibenzoyldiazomethane (DBDM) produced highly electrophilic benzoylketene via Wolff rearrangement. DBDM derivative possessing an aminoalkyl side chain induced a DNA cleavage selectively at guanine (G) residues upon photoirradiation and subsequent piperidine treatment. In order to devise photochemical DNA cleavers that can specifically alkylate a guanine residue proximal to the target sequence of long DNA fragments, a new reagent, DBDM-OSu, which facilitates the connection of DBDM unit to various DNA binders, was developed. DBDM-oligonucleotide (ODN) conjugates 5 and 6 were obtained by the coupling of 5‘-aminohexyl 8-mer [H2N-(CH2)6-d(ACGTCAGG)-3‘] and 15-mer [H2N-(CH2)6-d(ACGTCAGGTGGCACT)-3‘], respectively, with DBDM-OSu in aqueous acetonitrile in the presence of sodium bicarbonate. Photoirradiation of 5 and 6 in the presence of 25-mer 5‘-d(AGTGCCACCTGACGTCTG18CTCTCTC)-3‘ having a complementary sequence induced cross-linking of both oligomers. A distinct cleavage band at guanine residue...