期刊
CHEMBIOCHEM
卷 21, 期 17, 页码 2455-2466出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202000110
关键词
DNA; enzymatic stability; G-quadruplexes; kinetics; modified phosphate; thermal stability
资金
- School of Fundamental Sciences (Massey University)
- Cancer Society of New Zealand [15/07]
- Russian Foundation for Basic Research [18-515-05007, 18-515-57006, 18-29-09045]
A quaternary ammonium butylsulfonyl phosphoramidate group (N+) was designed to replace all the phosphates in a G-rich oligodeoxynucleotide d(TG(4)T), resulting in a formally charge-neutral zwitterionic N+TG(4)T sequence. We evaluated the effects of N+phosphate modifications on the structural, thermodynamic and kinetic properties of the parallel G-quadruplexes (G4) formed by TG(4)T and compared them to the properties of the recently published phosphoryl guanidine d(TG(4)T) (PG-TG(4)T). Using size-exclusion chromatography, we established that, unlike PG-TG(4)T, which exists as a mixture of complexes of different molecularity in solution, N+TG(4)T forms an individual tetramolecular complex. In contrast to PG modifications that destabilized G4s, the presence of N+ modifications increased thermal stability relative to unmodified [d(TG(4)T)](4). The initial stage of assembly of N+TG(4)T proceeded faster in the presence of Na+ than K(+)ions and, similarly to PG-TG(4)T, was independent of the salt concentration. However, after complex formation exceeded 75 %, N+TG(4)T in solution with Na(+)showed slower association than with K+. N+TG(4)T could also form G4s in solution with Li(+)ions at a very low strand concentration (10 mu M); something that has never been reported for the native d(TG(4)T). Charge-neutral PG-G4s can invade preformed native G4s, whereas no invasion was observed between N+and native G4s, possibly due to the increased thermal stability of [N+TG(4)T](4). The N+ modification makes d(TG(4)T) fully resistant to enzymatic digestion, which could be useful for intracellular application of N+-modified DNA or RNA.
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