TY - JOUR

T1 - Neutral and Negatively Charged Phosphate Modifications Altering Thermal Stability, Kinetics of Formation and Monovalent Ion Dependence of DNA G-Quadruplexes

AU - Su, Yongdong

AU - Fujii, Hirofumi

AU - Burakova, Ekaterina A.

AU - Chelobanov, Boris P.

AU - Fujii, Masayuki

AU - Stetsenko, Dmitry A.

AU - Filichev, Vyacheslav V.

N1 - Publisher Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2019/4/15

Y1 - 2019/4/15

N2 - The effect of phosphate group modifications on formation and properties of G-quadruplexes (G4s) has not been investigated in detail. Here, we evaluated the structural, thermodynamic and kinetic properties of the parallel G-quadruplexes formed by oligodeoxynucleotides d(G4T), d(TG4T) and d(TG5T), in which all phosphates were replaced with N-methanesulfonyl (mesyl) phosphoramidate or phosphoryl guanidine groups resulting in either negatively charged or neutral DNA sequences, respectively. We established that all modified sequences were able to form G-quadruplexes of parallel topology; however, the presence of modifications led to a decrease in thermal stability relative to unmodified G4s. In contrast to negatively charged G4s, assembly of neutral G4 DNA species was faster in the presence of sodium ions than potassium ions, and was independent of the salt concentration used. Formation of mixed G4s composed of both native and neutral G-rich strands has been detected using native gel electrophoresis, size-exclusion chromatography and ESI-MS. In summary, our results indicate that the phosphate modifications studied are compatible with G-quadruplex formation, which could be used for the design of biologically active compounds.

AB - The effect of phosphate group modifications on formation and properties of G-quadruplexes (G4s) has not been investigated in detail. Here, we evaluated the structural, thermodynamic and kinetic properties of the parallel G-quadruplexes formed by oligodeoxynucleotides d(G4T), d(TG4T) and d(TG5T), in which all phosphates were replaced with N-methanesulfonyl (mesyl) phosphoramidate or phosphoryl guanidine groups resulting in either negatively charged or neutral DNA sequences, respectively. We established that all modified sequences were able to form G-quadruplexes of parallel topology; however, the presence of modifications led to a decrease in thermal stability relative to unmodified G4s. In contrast to negatively charged G4s, assembly of neutral G4 DNA species was faster in the presence of sodium ions than potassium ions, and was independent of the salt concentration used. Formation of mixed G4s composed of both native and neutral G-rich strands has been detected using native gel electrophoresis, size-exclusion chromatography and ESI-MS. In summary, our results indicate that the phosphate modifications studied are compatible with G-quadruplex formation, which could be used for the design of biologically active compounds.

KW - DNA

KW - G-quadruplexes

KW - kinetics

KW - modified phosphates

KW - neutral backbones

KW - thermal stability

KW - PNA

KW - CD SPECTRA

KW - APTAMER

KW - HYBRIDIZATION

KW - COMPLEMENTARY

KW - INVASION

KW - SEQUENCE

KW - BINDING

KW - DERIVATIVES

KW - Oligodeoxyribonucleotides/chemistry

KW - Phosphates/chemistry

KW - Ions/chemical synthesis

KW - DNA/chemical synthesis

KW - Thermodynamics

KW - G-Quadruplexes

KW - Kinetics

UR - http://www.scopus.com/inward/record.url?scp=85060578772&partnerID=8YFLogxK

U2 - 10.1002/asia.201801757

DO - 10.1002/asia.201801757

M3 - Article

C2 - 30600926

AN - SCOPUS:85060578772

VL - 14

SP - 1212

EP - 1220

JO - Chemistry - An Asian Journal

JF - Chemistry - An Asian Journal

SN - 1861-4728

IS - 8

ER -