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.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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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)
- Urheber
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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
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:27 MESZ
Datenpartner
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Beteiligte
- Pomeislová, Alice
- Vrzal, Lukáš
- Kozák, Jaroslav
- Dobiaš, Juraj
- Hubálek, Martin
- Dvořáková, Hana
- Reyes‐Gutiérrez, Paul E.
- Teplý, Filip
- Veverka, Václav
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