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G4 Sensing Pyridyl‐Thiazole Polyamide Represses c‐KIT Expression in Leukemia Cells
Author(s) -
Paul Raj,
Dutta Debasish,
Das Tania,
Debnath Manish,
Dash Jyotirmayee
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202100907
Subject(s) - oncogene , polyamide , nucleic acid , g quadruplex , dna , thiazole , chemistry , microbiology and biotechnology , leukemia , cell , biology , cancer research , biochemistry , stereochemistry , genetics , cell cycle , organic chemistry
Specific sensing and functional tuning of nucleic acid secondary structures remain less explored to date. Herein, we report a thiazole polyamide TPW that binds specifically to c‐KIT1 G‐quadruplex (G4) with sub‐micromolar affinity and ∼1 : 1 stoichiometry and represses c‐KIT proto‐oncogene expression. TPW shows up to 10‐fold increase in fluorescence upon binding with c‐KIT1 G4, but shows weak or no quantifiable binding to other G4s and ds26 DNA . TPW can increase the number of G4‐specific antibody (BG4) foci and mark G4 structures in cancer cells. Cell‐based assays reveal that TPW can efficiently repress c‐KIT expression in leukemia cells via a G4‐dependent process. Thus, the polyamide can serve as a promising probe for G‐quadruplex recognition with the ability to specifically alter c‐KIT oncogene expression.