SEQUENCE SPECIFICITY OF PSORALEN PHOTOBINDING TO DNA - A QUANTITATIVE APPROACH

被引:18
作者
GIA, O
MAGNO, SM
GARBESI, A
COLONNA, FP
PALUMBO, M
机构
[1] UNIV PADUA,DEPT PHARMACEUT SCI,VIA MARZOLO 5,I-35131 PADUA,ITALY
[2] CNR,IST COMPOSTI CARBONIO CONTENENTI ETEROATOMI & LORO APPLICAZ,I-40064 OZZANO EMILIA,ITALY
[3] UNIV CAGLIARI,DEPT PHARM CHEM & TECHNOL,I-09100 CAGLIARI,ITALY
关键词
D O I
10.1021/bi00162a021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effects of different DNA sequences on the photoreaction of various furocoumarin derivatives was investigated from a quantitative point of view using a number of selfcomplementary oligonucleotides. These contained 5'-TA and 5'-AT residues, having various flanking sequences. The furocoumarins included classical bifunctional derivatives, such as 8-methoxy- and 5-methoxypsoralen, as well as monofunctional compounds, such as angelicin and benzopsoralen. Taking into an account the thermodynamic constant for noncovalent binding of each psoralen to each DNA sequence, the rate constants for the photobinding process to each fragment were evaluated. The extent of photoreaction is greatly affected by the DNA sequence examined. While sequences of the type 5'-(GTAC)n are quite reactive towards all furocoumarins, 5'-TATA exhibited a reduced rate of photobinding using monofunctional psoralens. In addition terminal 5'-TA groups were the least reactive with 5-and 8-methoxypsoralen, but not with angelicin or benzopsoralen. Also 5'-AT-containing fragments exhibited remarkably variable responses toward monofunctional or bifunctional psoralen derivatives. As a general trend the photoreactivity rate of the former is less sequence-sensitive, the ratio between maximum and minimum being less than 2 for the examined fragments. The same ratio is about 3.4 for 8-methoxypsoralen and 6.2 for 5-methoxypsoralen. This approach, in combination with footprinting studies, appears to be quite useful for a quantitative investigation of the process of covalent binding of psoralens to specific sites in DNA.
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页码:11818 / 11822
页数:5
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