Molecular engineering of G-quadruplex ligands based on solvent effect of polyethylene glycol.
Because various non-parallel G-quadruplexes of human telomeric sequences in K+ solution can be converted to a parallel G-quadruplex by adding polyethylene glycol (PEG) as a co-solvent, we have taken advantage of this property of PEG to study the covalent attachment of a PEG unit to a G-quadruplex ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC). The hybrid ligand with the PEG unit, BMVC-8C3O or BMVC-6C2O by substituting either the tetraethylene glycol or the triethylene glycol terminated with a methyl-piperidinium cation in N-9 position of BMVC, not only induces structural change from different non-parallel G-quadruplexes to a parallel G-quadruplex but also increases the melting temperature of human telomeres in K+ solution by more than 45°C. In addition, our ligand work provides further confidence that the local water structure plays the key to induce conformational change of human telomere.
Department of Chemistry, National Taiwan University, Academia Sinica, Taipei 106, Taiwan, ROC.
Zi-Fu
ZF
Wang
Ta-Chau
TC
Chang
D002227:Carbazoles / Q000737:chemistry*; D002942:Circular Dichroism; D054856:G-Quadruplexes; D008024:Ligands; D009691:Nucleic Acid Denaturation; D011092:Polyethylene Glycols / Q000737:chemistry; D011726:Pyridinium Compounds / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D016615:Telomere / Q000737:chemistry*
D002227:Carbazoles; D008024:Ligands; D011726:Pyridinium Compounds; D012997:Solvents; D011092:Polyethylene Glycols