Carbocyclic analogues of lexitropsin--DNA affinity and endonuclease inhibition.
A DNA-binding affinity and the effect on restriction enzymes activity of seven carbocyclic mono- and bis-lexitropsins and two analogues of pentamidine with unsubstituted N-terminal amine group were investigated. DNA association constants (Kapp) show that DNA affinity of mono-compounds is much weaker than netropsin and distamycin. Bis-analogues of netropsin bind DNA more strongly than mono-ligands, but without sequence-selectivity. Only pentamidine derivatives reveal preference to AT-rich sequence. The studied compounds can inhibit catalytical action of endonucleases recognizing sequence of four AT base pairs following one another.
Pućkowska
Anna
A
Department of Organic Chemistry, Medical University of Białystok, A. Mickiewicza 2a Str. 15-222 Białystok, Poland. pucanka@amb.edu.pl
Drozdowska
Danuta
D
Midura-Nowaczek
Krystyna
K
D000146:Acids, Carbocyclic / Q000737:chemistry*; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D006690:Bisbenzimidazole / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004214:Distamycins / Q000737:chemistry; D004720:Endonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015394:Molecular Structure; D009429:Netropsin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010419:Pentamidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D000146:Acids, Carbocyclic; D004214:Distamycins; C053654:lexitropsin; D009429:Netropsin; D010419:Pentamidine; C030000:stallimycin; D004247:DNA; D004720:Endonucleases; D006690:Bisbenzimidazole