We propose a bimolecular approach for G-quadruplex alkylation, using a pro-reactive furan-containing ligand, activated by red-light irradiation of a proximate G4-binding photosensitizer. G4- over dsDNA alkylation can be achieved selectively and proves high-yielding at low ligand excess. HPLC and modelling studies allowed identifying potential residues involved in the alkylation.
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http://dx.doi.org/10.1039/d0cc06030e | DOI Listing |
Elife
December 2024
Department of Pharmacology, Weill Medical College, Cornell University, New York, United States.
BMC Biol
September 2024
State Key Laboratory of Livestock and Poultry Breeding, & Lingnan Guangdong Laboratory of Agriculture, & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding & Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, South China Agricultural University, Guangzhou, 510642, China.
Sci Rep
August 2024
Division of Cancer (Epi-)Genetics, Department of Biosciences and Medical Biology, Center for Tumor Biology and Immunology (CTBI), Paris Lodron University Salzburg, Hellbrunnerstraße 34, 5020, Salzburg, Austria.
The alarming increase in global rates of metabolic diseases (MetDs) and their association with cancer risk renders them a considerable burden on our society. The interplay of environmental and genetic factors in causing MetDs may be reflected in DNA methylation patterns, particularly at non-canonical (non-B) DNA structures, such as G-quadruplexes (G4s) or R-loops. To gain insight into the mechanisms of MetD progression, we focused on DNA methylation and functional analyses on intragenic regions of two MetD risk genes, the glucokinase (GCK) exon 7 and the transmembrane 6 superfamily 2 (TM6SF2) intron 2-exon 3 boundary, which harbor non-B DNA motifs for G4s and R-loops.
View Article and Find Full Text PDFBioorg Med Chem Lett
September 2024
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan; Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan. Electronic address:
The role of G-quadruplex (G4) in cellular processes can be investigated by the covalent modification of G4-DNA using alkylating reagents. Controllable alkylating reagents activated by external stimuli can react elegantly and selectively. Herein, we report a chemical activation system that can significantly boost the reaction rate of methylamine-protected vinyl-quinazolinone (VQ) derivative for the alkylation of G4-DNA.
View Article and Find Full Text PDFNucleic Acids Res
July 2024
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Emerging evidence indicates that arginine methylation promotes the stability of arginine-glycine-rich (RGG) motif-containing RNA-binding proteins (RBPs) and regulates gene expression. Here, we report that post-translational modification of FXR1 enhances the binding with mRNAs and is involved in cancer cell growth and proliferation. Independent point mutations in arginine residues of FXR1's nuclear export signal (R386 and R388) and RGG (R453, R455 and R459) domains prevent it from binding to RNAs that form G-quadruplex (G4) RNA structures.
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