Double-stranded DNA minor groove at AT-rich sequences (DNA minor groove (AT-rich))

The minor groove of double-stranded DNA, specifically at sequences rich in adenine (A) and thymine (T), is a critical structural target for a variety of small-molecule ligands and proteins (nih.gov, 2000; oup.com, 1993). AT-rich regions are characterized by a narrow, deep groove and a well-defined spine of hydration, which provides a unique shape and electrostatic environment that favors the binding of crescent-shaped molecules through van der Waals forces and hydrogen bonding (nih.gov, 2012; atdbio.com). Biologically, these regions are essential for the binding of architectural proteins and transcription factors, such as the TATA-binding protein (TBP), which are necessary for the initiation of transcription and DNA replication (nih.gov, 2000; researchgate.net, 2025). Drugs targeting the AT-rich minor groove, known as minor groove binders (MGBs), can displace the spine of hydration and disrupt these vital protein-DNA interactions, leading to the inhibition of gene expression and cell cycle progression (researchgate.net, 2013; nih.gov, 2000). Clinically, MGBs like pentamidine and diminazene are used as antiparasitic agents, often targeting the AT-rich kinetoplast DNA in pathogens, while others like CC-1065 derivatives have been explored for cancer therapy (nih.gov, 2012; researchgate.net, 2012). However, the development of these agents is often limited by non-specific toxicity and potential genotoxicity due to their interaction with the host genome (nih.gov, 2012; nih.gov, 2000).

Other names

AT-rich DNA minor grooveMinor groove of B-DNAAT-tractsMinor groove of AT-rich DNA

Non-covalent binding to the minor groove of AT-rich DNA; displacement of the spine of hydration; competitive inhibition of DNA-binding proteins such as transcription factors; interference with DNA replication and transcription; induction of DNA damage and apoptosis.