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.
Department of Organic Chemistry, Medical University of Białystok, A. Mickiewicza 2a Str. 15-222 Białystok, Poland. pucanka@amb.edu.pl
Anna
A
Pućkowska
Danuta
D
Drozdowska
Krystyna
K
Midura-Nowaczek
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