8ABD

Solution structure of Phen-DC3 intercalating into a quadruplex-duplex hybrid

Summary for 8ABD

• Entry DOI: 10.2210/pdb8abd/pdb
• Related: 8ABN
• NMR Information: BMRB: 34740
• Descriptor: DNA (36-MER), N2,N9-bis(1-methylquinolin-3-yl)-1,10-phenanthroline-2,9-dicarboxamide (2 entities in total)
• Functional Keywords: g-quadruplex, duplex, quadruplex-duplex junction, intercalation, phen-dc3, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 11760.86

Authors

Vianney, Y.M.,Weisz, K. (deposition date: 2022-07-04, release date: 2022-11-02, Last modification date: 2024-05-15)

Primary citation

Vianney, Y.M.,Weisz, K.
High-affinity binding at quadruplex-duplex junctions: rather the rule than the exception.
Nucleic Acids Res., 50:11948-11964, 2022

PubMed Abstract: Quadruplex-duplex (Q-D) junctions constitute unique structural motifs in genomic sequences. Through comprehensive calorimetric as well as high-resolution NMR structural studies, Q-D junctions with a hairpin-type snapback loop coaxially stacked onto an outer G-tetrad were identified to be most effective binding sites for various polycyclic quadruplex ligands. The Q-D interface is readily recognized by intercalation of the ligand aromatic core structure between G-tetrad and the neighboring base pair. Based on the thermodynamic and structural data, guidelines for the design of ligands with enhanced selectivity towards a Q-D interface emerge. Whereas intercalation at Q-D junctions mostly outcompete stacking at the quadruplex free outer tetrad or intercalation between duplex base pairs to varying degrees, ligand side chains considerably contribute to the selectivity for a Q-D target over other binding sites. In contrast to common perceptions, an appended side chain that additionally interacts within the duplex minor groove may confer only poor selectivity. Rather, the Q-D selectivity is suggested to benefit from an extension of the side chain towards the exposed part of the G-tetrad at the junction. The presented results will support the design of selective high-affinity binding ligands for targeting Q-D interfaces in medicinal but also technological applications.

PubMed: 36416262
DOI: 10.1093/nar/gkac1088

Experimental method

SOLUTION NMR