THE ORIENTATION OF NORFLOXACIN BOUND TO DOUBLE-STRANDED DNA

Norfloxacin is a widely used antibacterial agent that inhibits DNA gyr ase. This fluoroquinolone drug has significant interaction with double -stranded DNA, as judged from absorption and circular dichroism measur ements. The mode of binding of norfloxacin to a variety of DNAs and po lynucleotides has been investigated by electric linear dichroism, In t he presence of calf thymus DNA, the drug chromophore is significantly tilted with respect to the DNA axis. This molecular arrangement contra dicts classical intercalation. The orientation of the quinolone drug v aries depending on the sequence of the target DNA, Binding to alternat ing copolymers is largely preferred compared to the corresponding homo polymers. The drug interacts preferentially with poly(dG-dC).(dG-dC) r ather than with the other polymucleotides. The deletion of the a-amino group of guanine (G-->I substitution) or the addition of a methyl gro up on cytosine residues (C-->methyl-C substitution) affect the drug-DN A interaction. The results show that norfloxacin is capable of interac ting with a variety of DNA sequences, possibly Via both minor and majo r groove contacts. (C) 1998 Academic Press.