Structural polymorphism is an extremely significant phenomenon of nucleic acids, in
which DNA and RNA oligonucleotide sequences are able to adapt various canonical, alternative and
multistranded structures. These alternative forms of DNA and RNA have an enormous potential of
participating in various cellular processes by recognizing ligands such as proteins, drugs and metal
ions in a sequence and structure-specific manner. Such DNA-ligand interactions prove to be highly
beneficial when exploited for therapeutic purposes. Many of these DNA/ RNA structures recognizing
drugs have already proved their potential as anticancer, antibacterial, anthelmintic and antiviral properties.
Over the last 2-3 decades, many mechanisms of DNA-drug interactions have been documented,
but still many other new mechanisms are being explored. Designing new drugs with improved
efficacy and specificity is of prime concern for all researchers which not only deals with the
experiments related to synthesizing drugs, but also takes care of searching novel routes or agents for
administration or delivery of these therapeutic agents by increasing their nuclear and cellular uptake.
This review aims at explaining the structural polymorphs/ multistranded DNA structures and their interactions
with pharmaceutical drugs in a structure-specific manner, along with their modes of interactions
and biological relevance. This detailed overview of multistranded DNA structures and interacting
drugs might further facilitate our understanding about molecular targets and drug development
in a more precise manner for the larger benefit of mankind.