1-硫代甲氧沙林和1-硫代补骨脂素：硫代补骨脂素的合成、光生物学性质及其与DNA的位点特异性反应

1-Thiomethoxsalen and 1-thiopsoralen: synthesis, photobiological properties, and site specific reaction of thiopsoralens with DNA.

作者信息

Jakobs A E, Piette J

机构信息

Laboratory of Heterocyclic Organic Chemistry (B6), University of Liège, Belgium.

出版信息

J Med Chem. 1995 Mar 17;38(6):869-74. doi: 10.1021/jm00006a003.

DOI:10.1021/jm00006a003

PMID:7699701

Abstract

The sulfur analogues of psoralen and 8-methoxypsoralen (8-MOP) in the pyrone moiety were synthesized and compared to the parent compounds in terms of photoreactivity with viral M13mp19 RF DNA. The damaged viral DNA was transfected into Escherichia coli and scored for infectivity toward Ca-treated wild-type E. coli. This allowed a comparative study of the sulfur and oxygen analogues to be made in terms of photoreactivity. Furthermore, the DNA sequence specificity for the formation of monoadducts and cross-links of the four analogues was determined with 32P-labeled oligonucleotides containing thymidine in different sequences. The most site specific of the studied psoralens is 8-MOP, while 1-thiopsoralen is the most reactive analogue. This new thio analogue of psoralen leads to the efficient formation of monoadducts and cross-links in any pyrimidine-purine site.

摘要

合成了补骨脂素和8-甲氧基补骨脂素（8-MOP）在吡喃酮部分的硫类似物，并就其与病毒M13mp19 RF DNA的光反应性与母体化合物进行了比较。将受损的病毒DNA转染到大肠杆菌中，并对其对经钙处理的野生型大肠杆菌的感染性进行评分。这使得能够就光反应性对硫和氧类似物进行比较研究。此外，使用含有不同序列胸腺嘧啶核苷的32P标记寡核苷酸确定了四种类似物形成单加合物和交联的DNA序列特异性。所研究的补骨脂素中位点特异性最高的是8-MOP，而1-硫代补骨脂素是反应性最强的类似物。这种新的补骨脂素硫类似物可在任何嘧啶-嘌呤位点高效形成单加合物和交联。