6FC9

The 1,8-bis(aminomethyl)anthracene and Quadruplex-duplex junction complex

Summary for 6FC9

• Entry DOI: 10.2210/pdb6fc9/pdb
• NMR Information: BMRB: 34221
• Descriptor: DNA (27-MER), [8-(azaniumylmethyl)anthracen-1-yl]methylazanium (2 entities in total)
• Functional Keywords: quadruplex, junction, non canonical dna strucute, ligand-dna complex, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 8683.73

Authors

Santana, A.,Serrano, I.,Montalvillo-Jimenez, L.,Corzana, F.,Bastida, A.,Jimenez-Barbero, J.,Gonzalez, C.,Asensio, J.L. (deposition date: 2017-12-20, release date: 2019-04-10, Last modification date: 2024-06-19)

Primary citation

Diaz-Casado, L.,Serrano-Chacon, I.,Montalvillo-Jimenez, L.,Corzana, F.,Bastida, A.,Santana, A.G.,Gonzalez, C.,Asensio, J.L.
De Novo Design of Selective Quadruplex-Duplex Junction Ligands and Structural Characterisation of Their Binding Mode: Targeting the G4 Hot-Spot.
Chemistry, 2020

PubMed Abstract: Targeting the interface between DNA quadruplex and duplex regions by small molecules holds significant promise in both therapeutics and nanotechnology. Herein, a new pharmacophore is reported, which selectively binds with high affinity to quadruplex-duplex junctions, while presenting a poorer affinity for G-quadruplex or duplex DNA alone. Ligands complying with the reported pharmacophore exhibit a significant affinity and selectivity for quadruplex-duplex junctions, including the one observed in the HIV-1 LTR-III sequence. The structure of the complex between a quadruplex-duplex junction with a ligand of this family has been determined by NMR methods. According to these data, the remarkable selectivity of this structural motif for quadruplex-duplex junctions is achieved through an unprecedented interaction mode so far unexploited in medicinal and biological chemistry: the insertion of a benzylic ammonium moiety into the centre of the partially exposed G-tetrad at the interface with the duplex. Further decoration of the described scaffolds with additional fragments opens up the road to the development of selective ligands for G-quadruplex-forming regions of the genome.

PubMed: 33368678
DOI: 10.1002/chem.202005026

Experimental method

SOLUTION NMR