Any therapeutic drug used for a disease whose pathology does not relate to DNA would bind with DNA anyway. In this case, is it desirable that the drug should be groove binder or intercalator so as to cause minimum alteration in DNA?
Prayasee Baruah
Well, firstly, it is quite wrong and a misconception that any therapeutic drug will eventually bind to DNA, it only occurs in the event of the drug target being nucleic acids. There exists other drugs which will only, and specifically target only specific metabolic, signaling enzymes and microtubules . Now to answer your question regarding Intercalator vs groove binder,
1. DNA intercalators are a group of compounds with diverse structure and the ability to bind firmly but reversibly to DNA by intercalation of a flat, aromatic chromophore between the base pairs. The only recognised forces that maintain the stability of the complex, even more than DNA alone, are van der Waals, hydrogen bonding, hydrophobic effects, and/or charge transfer forces. Classical intercalators have a straight, heteroaromatic ring which comes in between two neighbouring base pairs. Interaction leads to structural changes of the DNA molecule resulting in the partial unwinding of the DNA molecule and extension of DNA chain by one base pair.
2. Minor groove DNA binding compounds are a new family of antineoplastic drugs with representatives already in the process of clinical testing. The structure of these molecules is characterised by several connected aromatic rings that allow freedom of movement and torsion. Binders usually have a characteristic curved shape compatible with the DNA minor groove. This formed complex is stabilised with hydrophobic interactions. Also, DNA binders do not cause significant structural changes in the DNA molecule and no change to the DNA free energy structure. Only in cell level, DNA minor groove binders stop the cell cycle in its G2-M phase.
SO, THE END NOTE - keeping in mind the above points about the Intercalators and the groove binder, definitely Intercalating agents (and drugs) like amonafide, Pyrazolacridine etc pose a greater threat to the DNA as compared to Groove Binders.
I am attaching the links to certain research materials and articles which might help you for further reference and study,
Mišković K, et al. ANTINEOPLASTIC DNA BINDING COMPOUNDS
(https://hrcak.srce.hr/file/164833)
Kubota Y, et al. INTERCALATION AND GROOVE BINDING MODES
(https://academic.oup.com/nass/article-pdf/42/1/53/3753329/421053.pdf)@@
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