9 1994by Hurnana Press Inc. All rights of any nature whatsoeverreserved. 0273-2289/94/4701--0039504.40 Mechanism of DNA-Drug Interactions PRAKASH PRABHAKAR AND ARVIND M. KAYASTHA* School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India Received April 29, 1993; Accepted September 7, 1993 ABSTRACT Over the last two decades many strategies have been planned to design specific drugs for rare diseases to target their action at the DNA level. Advancements in our understanding of the interactions of small nonpeptide molecules with DNA have opened the doors for "rational" drug design. Special methods have now been developed to give accurate account of the precise location of ligand-DNA adducts on target DNA. We are now in a position to think of designing ligands that recognize particular sequences of base pairs. This work will allow us to enter into a new era of gene therapy for diseases like Cystic fibrosis, Alzheimer's disease and many related disorders at genetic level. These ligands can also be employed in the treatment of various types of cancers. They may also be useful as highly specific probes to locate particular sequences in the genomic DNA. Index Entries: Antibiotics; intercalators; pseudonuclease; bisin- tercalators; antitumor agents. INTRODUCTION There are certain drugs that are shown to effect the very vital func- tions of living organisms, such as protein biosynthesis, nucleic acid repli- cation and gene expression, collectively called antibiotics. Over the past 20 years, enormous advancement has been made in our understanding of the interaction of these small molecules (antibiotics) and in general cytotoxins, with DNA. The interest derived not only from *Author to whom all correspondence and reprint requests should be addressed. Applied Biochemistry and Biotechnology 39 Vol. 4 7, 1994