Research output: Contribution to journal › Article › peer-review
The Importance of Phosphates for DNA G-Quadruplex Formation : Evaluation of Zwitterionic G-Rich Oligodeoxynucleotides. / Su, Yongdong; Edwards, Patrick J.B.; Stetsenko, Dmitry A. et al.
In: ChemBioChem, Vol. 21, No. 17, 01.09.2020, p. 2455-2466.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - The Importance of Phosphates for DNA G-Quadruplex Formation
T2 - Evaluation of Zwitterionic G-Rich Oligodeoxynucleotides
AU - Su, Yongdong
AU - Edwards, Patrick J.B.
AU - Stetsenko, Dmitry A.
AU - Filichev, Vyacheslav V.
N1 - © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - A quaternary ammonium butylsulfonyl phosphoramidate group (N+) was designed to replace all the phosphates in a G-rich oligodeoxynucleotide d(TG4T), resulting in a formally charge-neutral zwitterionic N+TG4T sequence. We evaluated the effects of N+phosphate modifications on the structural, thermodynamic and kinetic properties of the parallel G-quadruplexes (G4) formed by TG4T and compared them to the properties of the recently published phosphoryl guanidine d(TG4T) (PG-TG4T). Using size-exclusion chromatography, we established that, unlike PG-TG4T, which exists as a mixture of complexes of different molecularity in solution, N+TG4T 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(TG4T)]4. The initial stage of assembly of N+TG4T proceeded faster in the presence of Na+ than K+ions and, similarly to PG-TG4T, was independent of the salt concentration. However, after complex formation exceeded 75 %, N+TG4T in solution with Na+showed slower association than with K+. N+TG4T could also form G4s in solution with Li+ions at a very low strand concentration (10 μM); something that has never been reported for the native d(TG4T). 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+TG4T]4. The N+ modification makes d(TG4T) fully resistant to enzymatic digestion, which could be useful for intracellular application of N+-modified DNA or RNA.
AB - A quaternary ammonium butylsulfonyl phosphoramidate group (N+) was designed to replace all the phosphates in a G-rich oligodeoxynucleotide d(TG4T), resulting in a formally charge-neutral zwitterionic N+TG4T sequence. We evaluated the effects of N+phosphate modifications on the structural, thermodynamic and kinetic properties of the parallel G-quadruplexes (G4) formed by TG4T and compared them to the properties of the recently published phosphoryl guanidine d(TG4T) (PG-TG4T). Using size-exclusion chromatography, we established that, unlike PG-TG4T, which exists as a mixture of complexes of different molecularity in solution, N+TG4T 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(TG4T)]4. The initial stage of assembly of N+TG4T proceeded faster in the presence of Na+ than K+ions and, similarly to PG-TG4T, was independent of the salt concentration. However, after complex formation exceeded 75 %, N+TG4T in solution with Na+showed slower association than with K+. N+TG4T could also form G4s in solution with Li+ions at a very low strand concentration (10 μM); something that has never been reported for the native d(TG4T). 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+TG4T]4. The N+ modification makes d(TG4T) fully resistant to enzymatic digestion, which could be useful for intracellular application of N+-modified DNA or RNA.
KW - DNA
KW - enzymatic stability
KW - G-quadruplexes
KW - kinetics
KW - modified phosphate
KW - thermal stability
KW - MOTIFS
KW - PNA
KW - STABILITY
KW - CD SPECTRA
KW - COMPLEMENTARY
KW - GUANOSINE-QUARTET STRUCTURE
KW - KINETICS
KW - SEQUENCE
KW - LOCKED NUCLEIC-ACIDS
KW - BINDING
UR - http://www.scopus.com/inward/record.url?scp=85084428131&partnerID=8YFLogxK
U2 - 10.1002/cbic.202000110
DO - 10.1002/cbic.202000110
M3 - Article
C2 - 32281223
AN - SCOPUS:85084428131
VL - 21
SP - 2455
EP - 2466
JO - ChemBioChem
JF - ChemBioChem
SN - 1439-4227
IS - 17
ER -
ID: 24281257