8ABN

Solution structure of a phenyl-indoloquinoline intercalating into a quadruplex-duplex hybrid

Summary for 8ABN

• Entry DOI: 10.2210/pdb8abn/pdb
• NMR Information: BMRB: 34741
• Descriptor: DNA (27-MER), diethyl-[3-[[4-(4,5,9-trimethyl-10H-indolo[3,2-b]quinolin-5-ium-11-yl)phenyl]carbonylamino]propyl]azanium (2 entities in total)
• Functional Keywords: g-quadruplex, duplex, quadruplex-duplex junction, indoloquinoline, intercalation, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 8940.07

Authors

Vianney, Y.M.,Weisz, K. (deposition date: 2022-07-04, release date: 2022-11-16, Last modification date: 2024-06-19)

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