Kinetic Target‐Guided Synthesis of Small‐Molecule G‐Quadruplex Stabilizers
Abstract: The formation of a G‐quadruplex motif in the promoter region of the c‐MYC protooncogene prevents its expression. Accordingly, G‐quadruplex stabilization by a suitable ligand may be a viable approach for anticancer therapy. In our study, we used the 4‐(4‐methylpiperazin‐1‐yl) aniline molecule, previously identified as a fragment library screen hit, as a template for the SAR‐guided design of a new small library of clickable fragments and subjected them to click reactions, including kinetic target‐guided synthesis in the presence of a G‐quadruplex forming oligonucleotide Pu24. We tested the clickable fragments and products of click reactions for their G‐quadruplex stabilizing activity and determined their mode of binding to the c‐MYC G‐quadruplex by NMR spectroscopy. The enhanced stabilizing potency of click products in biology assays (FRET, Polymerase extension assay) matched the increased yields of in situ click reactions. In conclusion, we identified the newly synthesized click products of bis‐amino derivatives of 4‐(4‐methylpiperazin‐1‐yl) aniline as potent stabilizers of c‐MYC G‐quadruplex, and their further evolution may lead to the development of an efficient tool for cancer treatment.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Kinetic Target‐Guided Synthesis of Small‐Molecule G‐Quadruplex Stabilizers ; volume:9 ; number:12 ; year:2020 ; pages:1236-1250 ; extent:15
ChemistryOpen ; 9, Heft 12 (2020), 1236-1250 (gesamt 15)
- Creator
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Pomeislová, Alice
Vrzal, Lukáš
Kozák, Jaroslav
Dobiaš, Juraj
Hubálek, Martin
Dvořáková, Hana
Reyes‐Gutiérrez, Paul E.
Teplý, Filip
Veverka, Václav
- DOI
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10.1002/open.202000261
- URN
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urn:nbn:de:101:1-2022062911102987308834
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:27 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Pomeislová, Alice
- Vrzal, Lukáš
- Kozák, Jaroslav
- Dobiaš, Juraj
- Hubálek, Martin
- Dvořáková, Hana
- Reyes‐Gutiérrez, Paul E.
- Teplý, Filip
- Veverka, Václav
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NMR investigations of G-quadruplex structures
Using Macrocyclic G‐Quadruplex Ligands to Decipher the Interactions Between Small Molecules and G‐Quadruplex DNA
Dicyanomethylene Squaraines: Aggregation and G-Quadruplex Complexation
Folding dynamics of polymorphic G-quadruplex structures
Identification of G-quadruplex clusters by high-throughput sequencing of whole-genome amplified products with a G-quadruplex ligand
Novel DNA Catalysts Based on G-Quadruplex Recognition
Corrigendum: Folding dynamics of polymorphic G-quadruplex structures
FANCJ promotes DNA synthesis through G‐quadruplex structures
G-Quadruplex Forming Repeat Sequences In Bacterial Genomes
The influence of G-quadruplex structures on meiosis
G‐Quadruplex Recognition by DARPIns through Epitope/Paratope Analogy **
Design, Synthesis, and Biophysical Characterization of Pyridine Bis‐Quinazoline Derivatives as Selective G‐Quadruplex DNA Stabilizers
NMR investigations of G-quadruplex structures
Using Macrocyclic G‐Quadruplex Ligands to Decipher the Interactions Between Small Molecules and G‐Quadruplex DNA
Dicyanomethylene Squaraines: Aggregation and G-Quadruplex Complexation
Folding dynamics of polymorphic G-quadruplex structures
Identification of G-quadruplex clusters by high-throughput sequencing of whole-genome amplified products with a G-quadruplex ligand
Novel DNA Catalysts Based on G-Quadruplex Recognition
Corrigendum: Folding dynamics of polymorphic G-quadruplex structures
FANCJ promotes DNA synthesis through G‐quadruplex structures
G-Quadruplex Forming Repeat Sequences In Bacterial Genomes
The influence of G-quadruplex structures on meiosis