A microgonotropen pentaaza pentabutylamine and its interactions with DNA.
The central pyrrole of a site-selective DNA minor groove binding tripyrrole peptide (1) has been attached to N-protected pentaazapentacosanoic acid (17) via a -(CH2)3-NHCO-(CH2)3- linker to provide 19, subsequent deprotection provided the pentaaza microgonotropen 4. The polyamine moiety of 4 reaches out of the minor groove and binds to the phosphate backbone of DNA. We find when employing Hoechst 33258 (Ht) as a fluorescent titrant to follow binding of 4 to the hexadecameric duplex d(GGCGCAAATTTGGCGG)/(CCGCCAAATTTGCGCC) and by 1H NMR titration of d(CGCAAATTTGCG)2 with 4 that the latter forms both 1:1 and 2:1 dsDNA complexes. Certain aspects of the structure of 4:d(CGCAAATTTGCG)2 complex derived via 1H NMR are discussed. The electrophoretic mobilities of phi X-174 DNA digested with HaeIII endonuclease restriction fragments complexed to 4 shows that the latter brings about a greater conformational change in the DNA fragments than observed previously with other microgonotropens.
Sengupta
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D
Department of Chemistry, University of California, Santa Barbara 93106, USA.
Blaskó
A
A
Bruice
T C
TC
D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004214:Distamycins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011522:Protons; D013057:Spectrum Analysis; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
D004214:Distamycins; D011522:Protons; D014157:Transcription Factors; C103713:microgonotropen pentaazapentabutylamine; D004247:DNA