G4LDB 2.2: a database for discovering and studying G-quadruplex and i-Motif ligands

Abstract

Noncanonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have attracted increasing research interests because of their unique structural and binding properties, as well as their important biological activities. To date, thousands of small molecules that bind to varying G4/iM structures have been designed, synthesized and tested for diverse chemical and biological uses. Because of the huge potential and increasing research interests on G4-targeting ligands, we launched the first G4 ligand database G4LDB in 2013. Here, we report a new version, termed G4LDB 2.2 (http://www.g4ldb.com), with upgrades in both content and function. Currently, G4LDB2.2 contains >3200 G4/iM ligands, ∼28 500 activity entries and 79 G4–ligand docking models. In addition to G4 ligand library, we have also added a brand new iM ligand library to G4LDB 2.2, providing a comprehensive view of quadruplex nucleic acids. To further enhance user experience, we have also redesigned the user interface and optimized the database structure and retrieval mechanism. With these improvements, we anticipate that G4LDB 2.2 will serve as a comprehensive resource and useful research toolkit for researchers across wide scientific communities and accelerate discovering and validating better binders and drug candidates.

Structured Waters Mediate Small Molecule Binding to G-Quadruplex Nucleic Acids

“…Docking studies were also undertaken within the G-quadruplex ligand database G4LDB 2.2 (https://www.g4ldb.com. Last accessed on 16 December 2021) [134], which utilizes the docking modules in AutoDock Vina 1.1.2 [135].…”

Ligands stimulating antitumour immunity as the next G-quadruplex challenge

“…Nevertheless, small molecules with high G4 affinity likely target multiple G4s in the genome leading to a wide and complex alteration of cellular transcriptomes. The diversity of this class of molecules is high (> 3000 compounds) [ 48 ], including also metal-containing compounds (as the organoplatinum complex Pt1, Table 2 ) with cell killing potential and ability to induce cell senescence [ 37 , 49 ]. However, studies focusing on G4-binder genome-wide effects are still a low number.…”

Genetic and Histopathological Heterogeneity of Neuroblastoma and Precision Therapeutic Approaches for Extremely Unfavorable Histology Subgroups

“…Interestingly, the MYCN promoter also possesses G4 sequences [ 68 ], suggesting that G4 stabilizers can target both MYC and MYCN . To date, several more potent G4 stabilizers have been reported [ 80 , 81 , 82 , 83 , 84 ], including the synthetic fluoroquinolone, Quarfloxin (CX-3543), which was developed for its ability to interact with the MYC G4 sequences [ 69 ]. However, it turns out that CX-3543 is preferentially concentrated in the nucleoli of cancer cells and inhibits rRNA transcription by RNA Pol I, not at the MYC locus [ 85 ].…”