期刊
CHEMBIOCHEM
卷 19, 期 5, 页码 505-512出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201700593
关键词
calorimetry; G-quadruplexes; indoloquinolines; NMR spectroscopy; sandwich complexes
资金
- Deutsche Forschungsgemeinschaft [INST 292/138-1]
Binding of an indoloquinoline derivative with an aminoalkyl side chain to a truncated sequence from the MYC promoter region was studied through isothermal titration calorimetry (ITC). The targeted MYC3 sequence lacks 3-flanking nucleotides and forms a monomeric parallel quadruplex (G4) with a blunt-ended 3-outer tetrad under the solution conditions employed. Analysis of ITC isotherms reveals multiple binding equilibria with the initial formation of a 1:2 ligand/quadruplex complex. Evaluation of electrophoretic mobilities as well as NMR spectral data confirm ligand-induced dimerization of MYC3 quadruplexes with the ligand sandwiched between the two 3-outer tetrads. Additional ligand molecules in excess bind to the 5-outer tetrads of the sandwich complex. Such a ligand-promoted G4 dimerization may be exploited for the controlled assembly or disassembly of G4 aggregates to expand on present quadruplex-based technologies.
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