A microgonotropen branched decaaza decabutylamine and its DNA and DNA transcription factor interactions

被引:20
作者
Bruice, TC [1 ]
Sengupta, D [1 ]
Blasko, A [1 ]
Chiang, SY [1 ]
Beerman, TA [1 ]
机构
[1] ROSWELL PK CANC INST,DEPT EXPT THERAPEUT,BUFFALO,NY 14263
关键词
D O I
10.1016/S0968-0896(97)00011-4
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 central pyrrole of a site selective DNA minor groove binding tripyrrole peptide 1 has been attached to a branched decaaza decabutylamine via a -(CH2)(3)-NHCO-(CH2)(3)- linker to provide the decaaza-microgonotropen (8). The decaaza decabutylamine moiety of 8 was designed to have a much greater affinity to the phosphodiester linkages of the backbone of DNA. Employing Hoechst 33258 (I-It) as a fluorescent titrant, the equilibrium constants for the binding of 8 to the hexadecameric duplex d(GGCGCA(3)T(3)GGCGG)/d(CCGCCA(3)T(3)GCGCC) and to calf thymus DNA were determined. The log of the product of equilibrium constants (log KL1KL2) for 1:1 and 1:2 complexes formation at A(3)T(3) is 17 (35 degrees C). Results of studies of the inhibition of the binding of several proteins to target DNA are discussed. Binding of the E2F1 transcription factor to its DNA target is 50% inhibited at similar to 2 nM concentration of 8. (C) 1997 Elsevier Science Ltd.
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页码:685 / 692
页数:8
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