Comb-type copolymer: stabilization of triplex DNA and possible application in antigene strategy.

  title={Comb-type copolymer: stabilization of triplex DNA and possible application in antigene strategy.},
  author={Anwarul Ferdous and H. Watanabe and Toshihiro Akaike and Atsushi Maruyama},
  journal={Journal of pharmaceutical sciences},
  volume={87 11},
By employing a reductive amination reaction between the epsilon-amino groups of poly(L-lysine) (PLL) and the reductive ends of the hydrophilic dextran (Dex) side chain, we have prepared different comb-type copolymers which varied in the degree of grafting and the length of the hydrophilic Dex chains. The resulting copolymers, poly(L-lysine)-graft-dextran (PLL-g-Dex), were tested for their ability to stabilize triplex DNA in vitro under physiologically relevant conditions. Thermal denaturation… 
Cationic copolymer-chaperoned short-armed 10–23 DNAzymes
The cationic copolymer poly(L-lysine)-graft-dextran (PLL-g-Dex) has nucleic acid chaperone-like activity that promotes DNAzyme reactivity and turnover efficacy, and maximally accelerated the reaction rate by 250-fold compared to the rate in the absence ofCopolymer.
Poly(l-lysine)-graft-dextran Copolymer Promotes Pyrimidine Motif Triplex DNA Formation at Physiological pH
The results certainly support the idea that the PLL-g-Dex copolymer could be a key material and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.
Comb-type cationic copolymer expedites DNA strand exchange while stabilizing DNA duplex.
The stabilization of strand exchange intermediates consisting of the parent duplex and the single strand by the copolymer is believed to be responsible for the observed acceleration behavior.
Synergistic stabilization of nucleic acid assembly by 2'-O,4'-C-methylene-bridged nucleic acid modification and additions of comb-type cationic copolymers.
Kinetic analyses revealed that the successful synergistic stabilization of triplex resulted from kinetic complementarity between increased association rate constants by the copolymer and decreased dissociation rate constant by the 2',4'-BNA modification.
End-grafted Sugar Chains as Aqueous Lubricant Additives: Synthesis and Macrotribological Tests of Poly(l-lysine)-graft-Dextran (PLL-g-dex) Copolymers
Comb-like graft copolymers with carbohydrate side chains have been developed as aqueous lubricant additives for oxide-based tribosystems, in an attempt to mimic biological lubrication systems, whose
Promotion of duplex and triplex DNA formation by polycation comb-type copolymers.
Although the purine motif triplex is pH-independent, triplexes involving guanine-rich TFOs are inhibited by physiological concentrations of certain monovalent cations (M(+)), especially K(+)).
Targeted gene delivery to sinusoidal endothelial cells: DNA nanoassociate bearing hyaluronan‐glycocalyx
  • Y. TakeiA. Maruyama N. Sato
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2004
The new PLL‐g‐ HA/DNA carrier system permits targeted transfer of exogenous genes selectively to the SECs and effectively stabilized DNA triplex formation.
Optimization of the Formulation and Design of Oligonucleotide-based Pharmaceuticals for the Purpose of Gene Therapy
The possibility to synthesize Zorro as a bi-directional single-stranded ON was investigated, thus reducing the size, facilitating the design and improving Zorra efficiency and these findings may represent a step in the development of ON-based drug products as a new class of therapeutics.
Development of biomaterials for gene therapy.
This review explores the conceptual and experimental aspects of polymer-based gene delivery and presents an overview on the recent use of polymers to enhance the effectiveness of plasmid-based systems.
copolymer accelerates DNA hybridization by two orders.
Poly(l-lysine)-graft-dextran at nanomolar concentration significantly accelerated DNA-hybridization rate over 200-fold under physiologically relevant ionic conditions.


Characterization of interpolyelectrolyte complexes between double-stranded DNA and polylysine comb-type copolymers having hydrophilic side chains.
By regulating the degree of grafting and the molecular weight of grafted side chains, it would be possible to design novel different graft copolymers capable of acting as carriers of functional genes to target cells or tissue.
Poly(L-lysine)-graft-dextran copolymer: amazing effects on triplex stabilization under physiological pH and ionic conditions (in vitro).
It is suggested that the ability of the graft copolymer to stabilize triplex DNA under physiologically relevant pH and salt concentrations will be a cue for further progress in the antigene strategy.
Synthesis of novel polyampholyte comb-type copolymers consisting of a poly(L-lysine) backbone and hyaluronic acid side chains for a DNA carrier.
These polyampholyte comb-type copolymers vary their assembling structure in water in response to two kinds of environmental factors, i.e., ionic strength and pH.
Conjugates of Oligonucleotides with Triplex-Specific Intercalating Agents. Stabilization of Triple-Helical DNA in the Promoter Region of the Gene for the α-Subunit of Interleukin 2 (IL-2Rα)
Triplex-specific intercalators, namely benzopyridoindole and BPQ derivatives, have been conjugated to the 5‘ end or to an internucleotide position of a 15-mer oligonucleotide and found to form and stabilize a triple-helical structure involving a 42-mer duplex target.
Selectivity of polyamines in triplex DNA stabilization.
Dinopropane stabilized the triplex DNA such that the Tm1 was 10 degrees C higher than that in the presence of an equimolar concentration of putrescine, and H2N (CH2)nNH2 was the most effective diamine to stabilize the poly(dA).2poly(dT) triplex.
Stabilization of triple helical DNA by a benzopyridoquinoxaline intercalator.
Evidence is obtained that BPQ is actually bound to the triplex region and may distort in a sequence-specific fashion, and in vivo BPQ might enhance the formation of both undesired and desired DNA triplexes.
Positively Charged Oligonucleotides Overcome Potassium-Mediated Inhibition of Triplex DNA Formation
It is concluded that replacement of phosphodiester bonds with positively-charged phosphoramidate linkages results in more efficient triplex formation, suggesting that these compounds may prove useful for in vivo applications.
The anti-gene strategy: control of gene expression by triplex-forming-oligonucleotides.
The results presently available provide a rational basis for the development of new tools for cellular biology and of new therapeutical approaches to selectively control gene expression at the transcriptional level.
Triplex DNA structures.
Intramolecular triplexes are the major elements of H-DNAs, unusual DNA structures, which are formed in homopurine-homopyrimidine regions of supercoiled DNAs.