The design and synthesis of 2,6-diphenylthiazolo[3,2-b][1,2,4]triazoles characterized by a large aromatic building block bearing cationic side chains are reported. These molecules are evaluated as telomeric G-quadruplex stabilizers and for their selectivity towards duplex DNA by competition experiments. Two compounds (14a, 19) were found active with high selectivity for telomeric G-quadruplex over duplex DNA.
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http://dx.doi.org/10.1016/j.bmcl.2009.05.025 | DOI Listing |
Bioorg Med Chem Lett
December 2024
Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, HarBin Medical University, Harbin, PR China. Electronic address:
The telomeric G-quadruplex (G4) along with the telomerase catalytic subunit hTERT are crucial in the extension of telomeres. Tumor cells can establish replicative immortality by activating the telomere-maintenance mechanism (TMM).Small molecule ligands can limit cancer telomere lengthening by by targeting at G4 and hTERT.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Biology, Penn State University, University Park, PA 16802, USA.
Non-canonical (non-B) DNA structures-e.g., bent DNA, hairpins, G-quadruplexes, Z-DNA, etc.
View Article and Find Full Text PDFBiochemistry
December 2024
High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
Telomere repeat-binding factor 2 (TRF2) is a key component of the shelterin complex which guards the integrity of the telomere. Most of the TRF2 discussed previously was focused on the telomere, and relatively less is discussed on aspects other than that. It is proved that TRF2 also localizes to other potential G-quadruplex-forming sequences among the whole genome besides the telomere.
View Article and Find Full Text PDFFEBS Lett
December 2024
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Genome maintenance is essential for the integrity of the genetic blueprint, of which only a small fraction is transcribed in higher eukaryotes. DNA lesions occurring in the transcribed genome trigger transcription pausing and transcription-coupled DNA repair. There are two major transcription-coupled DNA repair pathways.
View Article and Find Full Text PDFBiochimie
December 2024
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia. Electronic address:
Except for telomeres, G4 DNA structures in the human genome can be formed only within the context of double-stranded DNA. DNA duplexes flanking the G4 structure may potentially affect the G4 architecture and the binding of G4-specific ligands. Here, we examine the interaction of TMPyP4, NMM, and PDS ligands with three structures formed by the same DNA fragment containing the (GGGT) sequence: the G4 in duplex (dsG4), G4 in single-stranded DNA (ssG4) and perfect duplex DNA (ds).
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