Mechanism of intermolecular purine-purine-pyrimidine triple helix stabilization by comb-type polylysine graft copolymer at physiologic potassium concentration

Anwarul Ferdous, Toshihiro Akaike, Atsushi Maruyama

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We previously reported a novel strategy to stabilize purine motif triplex DNA within a mammalian gene promoter at physiologically relevant pH, temperature, and potassium (K+) concentrations by a comb-type poly(L-lysine)-graft-dextran copolymer [Ferdous et al., (1998) Nucleic Acids Res. 26, 3949-3954]. Here we describe the major contribution(s) of the copolymer to stabilize the purine motif triplex DNA at physiological K+ concentrations. Self-aggregation through guanine-quartet formation of guanine-rich (G-rich) triplex-forming oligonucleotides (TFOs) has long been proposed for K+-mediated inhibition of the purine motif triplex formation. However, this was not the case for the severe inhibitory effect of K+ observed under our reaction conditions. Rather significant decrease in rate of triplex formation involving a G-rich TFO was a major factor to confer K+ inhibition. Interestingly, in the presence of the copolymer the rate of triplex formation was tremendously increased and K+-induced dissociation of preformed triplexes was not observed. Moreover, the triplex-promoting/stabilizing efficiency of the copolymer was amazingly higher than that of physiological concentrations of spermine. An absolute increase in binding constant of the TFO to the target duplex could therefore be the predominant mechanistic source for the copolymer-mediated triplex stabilization under physiological conditions in vitro.

Original languageEnglish (US)
Pages (from-to)520-526
Number of pages7
JournalBioconjugate Chemistry
Volume11
Issue number4
DOIs
StatePublished - Jul 2000

Fingerprint

Comb and Wattles
Polylysine
Graft copolymers
Oligonucleotides
Potassium
Guanine
Copolymers
Stabilization
Transplants
G-Quadruplexes
Spermine
DNA
Nucleic Acids
Dextran
Nucleic acids
Temperature
Agglomeration
Grafts
Genes
purine

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Mechanism of intermolecular purine-purine-pyrimidine triple helix stabilization by comb-type polylysine graft copolymer at physiologic potassium concentration. / Ferdous, Anwarul; Akaike, Toshihiro; Maruyama, Atsushi.

In: Bioconjugate Chemistry, Vol. 11, No. 4, 07.2000, p. 520-526.

Research output: Contribution to journalArticle

@article{fd3e791008a24237a6d12f6b9d1a3385,
title = "Mechanism of intermolecular purine-purine-pyrimidine triple helix stabilization by comb-type polylysine graft copolymer at physiologic potassium concentration",
abstract = "We previously reported a novel strategy to stabilize purine motif triplex DNA within a mammalian gene promoter at physiologically relevant pH, temperature, and potassium (K+) concentrations by a comb-type poly(L-lysine)-graft-dextran copolymer [Ferdous et al., (1998) Nucleic Acids Res. 26, 3949-3954]. Here we describe the major contribution(s) of the copolymer to stabilize the purine motif triplex DNA at physiological K+ concentrations. Self-aggregation through guanine-quartet formation of guanine-rich (G-rich) triplex-forming oligonucleotides (TFOs) has long been proposed for K+-mediated inhibition of the purine motif triplex formation. However, this was not the case for the severe inhibitory effect of K+ observed under our reaction conditions. Rather significant decrease in rate of triplex formation involving a G-rich TFO was a major factor to confer K+ inhibition. Interestingly, in the presence of the copolymer the rate of triplex formation was tremendously increased and K+-induced dissociation of preformed triplexes was not observed. Moreover, the triplex-promoting/stabilizing efficiency of the copolymer was amazingly higher than that of physiological concentrations of spermine. An absolute increase in binding constant of the TFO to the target duplex could therefore be the predominant mechanistic source for the copolymer-mediated triplex stabilization under physiological conditions in vitro.",
author = "Anwarul Ferdous and Toshihiro Akaike and Atsushi Maruyama",
year = "2000",
month = "7",
doi = "10.1021/bc990166t",
language = "English (US)",
volume = "11",
pages = "520--526",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - Mechanism of intermolecular purine-purine-pyrimidine triple helix stabilization by comb-type polylysine graft copolymer at physiologic potassium concentration

AU - Ferdous, Anwarul

AU - Akaike, Toshihiro

AU - Maruyama, Atsushi

PY - 2000/7

Y1 - 2000/7

N2 - We previously reported a novel strategy to stabilize purine motif triplex DNA within a mammalian gene promoter at physiologically relevant pH, temperature, and potassium (K+) concentrations by a comb-type poly(L-lysine)-graft-dextran copolymer [Ferdous et al., (1998) Nucleic Acids Res. 26, 3949-3954]. Here we describe the major contribution(s) of the copolymer to stabilize the purine motif triplex DNA at physiological K+ concentrations. Self-aggregation through guanine-quartet formation of guanine-rich (G-rich) triplex-forming oligonucleotides (TFOs) has long been proposed for K+-mediated inhibition of the purine motif triplex formation. However, this was not the case for the severe inhibitory effect of K+ observed under our reaction conditions. Rather significant decrease in rate of triplex formation involving a G-rich TFO was a major factor to confer K+ inhibition. Interestingly, in the presence of the copolymer the rate of triplex formation was tremendously increased and K+-induced dissociation of preformed triplexes was not observed. Moreover, the triplex-promoting/stabilizing efficiency of the copolymer was amazingly higher than that of physiological concentrations of spermine. An absolute increase in binding constant of the TFO to the target duplex could therefore be the predominant mechanistic source for the copolymer-mediated triplex stabilization under physiological conditions in vitro.

AB - We previously reported a novel strategy to stabilize purine motif triplex DNA within a mammalian gene promoter at physiologically relevant pH, temperature, and potassium (K+) concentrations by a comb-type poly(L-lysine)-graft-dextran copolymer [Ferdous et al., (1998) Nucleic Acids Res. 26, 3949-3954]. Here we describe the major contribution(s) of the copolymer to stabilize the purine motif triplex DNA at physiological K+ concentrations. Self-aggregation through guanine-quartet formation of guanine-rich (G-rich) triplex-forming oligonucleotides (TFOs) has long been proposed for K+-mediated inhibition of the purine motif triplex formation. However, this was not the case for the severe inhibitory effect of K+ observed under our reaction conditions. Rather significant decrease in rate of triplex formation involving a G-rich TFO was a major factor to confer K+ inhibition. Interestingly, in the presence of the copolymer the rate of triplex formation was tremendously increased and K+-induced dissociation of preformed triplexes was not observed. Moreover, the triplex-promoting/stabilizing efficiency of the copolymer was amazingly higher than that of physiological concentrations of spermine. An absolute increase in binding constant of the TFO to the target duplex could therefore be the predominant mechanistic source for the copolymer-mediated triplex stabilization under physiological conditions in vitro.

UR - http://www.scopus.com/inward/record.url?scp=0033879865&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033879865&partnerID=8YFLogxK

U2 - 10.1021/bc990166t

DO - 10.1021/bc990166t

M3 - Article

C2 - 10898573

AN - SCOPUS:0033879865

VL - 11

SP - 520

EP - 526

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 4

ER -