Double-stranded DNA (5′-PuGATCPy-3′ sequence) (dsDNA (PuGATCPy))

Double-stranded DNA containing the 5′-PuGATCPy-3′ sequence (where Pu represents a purine and Py represents a pyrimidine) is a specific genomic motif that serves as a high-affinity binding site for certain anthracycline antibiotics, most notably nogalamycin and its semi-synthetic derivative menogaril (Searle et al., 1988, Biochemistry). This hexanucleotide sequence is characterized by its ability to accommodate the threading intercalation of these drugs, where the planar chromophore inserts between base pairs while bulky amino-sugar groups occupy both the major and minor grooves of the DNA helix (Williams et al., 1990, PNAS). Biologically, the formation of these stable DNA-drug complexes at PuGATCPy sites interferes with critical cellular processes, including DNA replication and RNA transcription, by physically blocking the progression of polymerase enzymes and inhibiting the activity of topoisomerases (PubChem, CID 119045). In the context of disease, this target is primarily relevant to oncology, as the disruption of DNA integrity and function leads to cell cycle arrest and apoptosis in rapidly proliferating cancer cells (National Cancer Institute). However, the therapeutic use of agents targeting these sequences is often limited by significant safety concerns, including myelosuppression and potential cardiotoxicity, which are common side effects of DNA-intercalating anthracyclines (StatPearls, Anthracyclines).

Other names

PuGATCPy DNA motifNogalamycin binding site5'-d(PuGATCPy)-3' sequenceHexanucleotide DNA intercalation site

DNA intercalation and simultaneous major/minor groove binding, leading to inhibition of DNA/RNA polymerase progression and topoisomerase activity.