6FC9

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

6FC9 の概要

• エントリーDOI: 10.2210/pdb6fc9/pdb
• NMR情報: BMRB: 34221
• 分子名称: DNA (27-MER), [8-(azaniumylmethyl)anthracen-1-yl]methylazanium (2 entities in total)
• 機能のキーワード: quadruplex, junction, non canonical dna strucute, ligand-dna complex, dna
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8683.73

構造登録者

Santana, A.,Serrano, I.,Montalvillo-Jimenez, L.,Corzana, F.,Bastida, A.,Jimenez-Barbero, J.,Gonzalez, C.,Asensio, J.L. (登録日: 2017-12-20, 公開日: 2019-04-10, 最終更新日: 2024-06-19)

主引用文献

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

実験手法

SOLUTION NMR