Custom G4 Microarrays Reveal Selective G-Quadruplex Recognition of Small Molecule BMVC: A Large-Scale Assessment of Ligand Binding Selectivity.
BMVC
G-quadruplex
G4
MYC
ligand selectivity
microarray
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
30 Jul 2020
30 Jul 2020
Historique:
received:
29
06
2020
revised:
24
07
2020
accepted:
25
07
2020
entrez:
6
8
2020
pubmed:
6
8
2020
medline:
20
3
2021
Statut:
epublish
Résumé
G-quadruplexes (G4) are considered new drug targets for human diseases such as cancer. More than 10,000 G4s have been discovered in human chromatin, posing challenges for assessing the selectivity of a G4-interactive ligand. 3,6-bis(1-Methyl-4-vinylpyridinium) carbazole diiodide (BMVC) is the first fluorescent small molecule for G4 detection in vivo. Our previous structural study shows that BMVC binds to the MYC promoter G4 (MycG4) with high specificity. Here, we utilize high-throughput, large-scale custom DNA G4 microarrays to analyze the G4-binding selectivity of BMVC. BMVC preferentially binds to the parallel MycG4 and selectively recognizes flanking sequences of parallel G4s, especially the 3'-flanking thymine. Importantly, the microarray results are confirmed by orthogonal NMR and fluorescence binding analyses. Our study demonstrates the potential of custom G4 microarrays as a platform to broadly and unbiasedly assess the binding selectivity of G4-interactive ligands, and to help understand the properties that govern molecular recognition.
Identifiants
pubmed: 32751510
pii: molecules25153465
doi: 10.3390/molecules25153465
pmc: PMC7436161
pii:
doi:
Substances chimiques
3,6-bis(1-methyl-4-vinylpyridium)carbazole diiodide
0
Carbazoles
0
Fluorescent Dyes
0
Ligands
0
MYC protein, human
0
Proto-Oncogene Proteins c-myc
0
Pyridinium Compounds
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA023168
Pays : United States
Organisme : NIH HHS
ID : P30CA023168
Pays : United States
Organisme : NIH HHS
ID : R01CA177585
Pays : United States
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