DNA MINOR-GROOVE RECOGNITION PROPERTIES OF PENTAMIDINE AND ITS ANALOGS - A MOLECULAR MODELING STUDY

A molecular mechanics and molecular dynamics approach has been used to examine the structure of the complex formed between pentamidine and t he d(CGCGAATTCGCG)2 duplex. Similar energy calculations have also been performed on complexes with closely related pentamidine analogs, usin g the complex with the parent drug as the starting point. The resultin g structures of the drug-DNA complexes and their energetics have been examined and are compared with the reported DNA binding affinities. Th ese studies provide rationalizations for the differences in binding be havior of pentamidine analogs with differing linker chain lengths and aromatic ring substitutions.