Theoretical models of pentamidine analogs activity based on their DNA minor groove complexes.
The B-DNA binding property of pentamidine analogs was analyzed employing molecular dynamic simulations and UV-vis absorption spectroscopy. Their AATT and ATAT sequence preferences were also examined. In theoretical energy computations, we considered two solvation models: the implicit model I, where the solvent is characterized by a dielectric constant and the explicit model E, where water molecules are treated as discrete entities. The binding energy correlates well with the increase of melting temperature of the 5'-d(CGCGAATTCGCG)(2)-3' and 5'-d(CGCGATATCGCG)(2)-3' dodecamers after complexation with ligands (DeltaTm), and deduced models predicted adequately the DNA affinities of the studied diamidines.
Zołek
Teresa
T
Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1 Str., 02 097 Warsaw, Poland.
Maciejewska
Dorota
D
D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D010419:Pentamidine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013696:Temperature
D010419:Pentamidine; D004247:DNA