1-Thiomethoxsalen and 1-thiopsoralen: synthesis, photobiological properties, and site specific reaction of thiopsoralens with DNA.
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.
Jakobs
A E
AE
Laboratory of Heterocyclic Organic Chemistry (B6), University of Liège, Belgium.
Piette
J
J
D001483:Base Sequence; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D003432:Cross-Linking Reagents; D018736:DNA Adducts / Q000096:biosynthesis; D004249:DNA Damage; D004279:DNA, Viral / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000821:virology; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000494:pharmacology*; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008969:Molecular Sequence Data; D010100:Oxygen / Q000494:pharmacology; D011701:PUVA Therapy; D010761:Phosphorus Radioisotopes; D018462:Photobiology; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D014162:Transfection
C092757:1-thiomethoxsalen; C092758:1-thiopsoralen; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D004279:DNA, Viral; D011564:Furocoumarins; D010761:Phosphorus Radioisotopes; D011838:Radiation-Sensitizing Agents; D010100:Oxygen; D002118:Calcium; D008730:Methoxsalen