AT-rich double-stranded B-form DNA (AT-rich dsDNA)

AT-rich double-stranded B-form DNA refers to genomic regions characterized by a high density of adenine-thymine base pairs that maintain the standard right-handed helical B-conformation. These sequences are structurally distinct due to a narrower and deeper minor groove compared to GC-rich regions, which creates a specific electrostatic and steric environment favorable for the binding of small-molecule ligands (PMID: 11513575). Biologically, AT-rich tracts are critical components of promoter regions (such as TATA boxes), origins of replication, and scaffold/matrix attachment regions (SARs/MARs), where they facilitate DNA melting and serve as docking sites for regulatory proteins (PMID: 15109166). In therapeutic contexts, these regions are targeted by minor groove binders (MGBs) like pentamidine and distamycin derivatives to treat parasitic infections and certain cancers by disrupting DNA-protein interactions and inhibiting essential cellular processes like transcription and replication (PubChem CID 4735). However, the clinical application of drugs targeting AT-rich DNA is often challenged by limited sequence selectivity, which can result in significant genotoxicity and off-target systemic toxicity (PMID: 12135515).

Other names

Adenine-thymine rich DNAAT-tractsDNA minor groove (AT-specific)B-DNA AT-rich regionsMinor groove of AT-rich DNA

Drugs typically act as minor groove binders (MGBs) that non-covalently associate with the narrow, deep minor groove of AT-rich sequences through hydrogen bonding, van der Waals forces, and electrostatic interactions. This binding displaces essential DNA-binding proteins (such as transcription factors and TATA-binding proteins), inhibits DNA-processing enzymes like topoisomerases and helicases, and can induce structural distortions that trigger DNA damage responses or inhibit replication and transcription (PMID: 11513575; PMID: 15109166).