Document Detail


Synergistic stabilization of nucleic acid assembly by 2'-O,4'-C-methylene-bridged nucleic acid modification and additions of comb-type cationic copolymers.
MedLine Citation:
PMID:  19170613     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Stabilization of nucleic acid assemblies, such as duplex and triplex, is quite important for their wide variety of potential applications. Various stabilization methods, including molecular designs of chemically modified nucleotides and hybrid stabilizers, and combinations of different stabilization methods have been developed to increase stability of nucleic acid assemblies. However, combinations of two stabilizing methods have not always yielded desired synergistic effects. In the present study, to propose a strategy for selection of a rational combination of stabilizing methods, we demonstrate synergistic stabilization of triplex by 2'-O,4'-C-methylene-bridged nucleic acid (2',4'-BNA) modification of triplex-forming oligonucleotide and addition of poly(l-lysine)-graft-dextran copolymer [poly(l-lysine) grafted with hydrophilic dextran side chains]. Each of these methods increased the binding constant for triplex formation by nearly 2 orders of magnitude. However, their kinetic contributions were quite distinct. The copolymer increased the association rate constant, whereas the 2',4'-BNA modification decreased the dissociation rate constant for triplex stabilization. The combination of both stabilizing methods increased the binding constant by nearly 4 orders of magnitude. Kinetic analyses revealed that the successful synergistic stabilization resulted from kinetic complementarity between increased association rate constants by the copolymer and decreased dissociation rate constants by the 2',4'-BNA modification. The stabilizing effect of one stabilization method did not alter that of the other stabilization method. We propose that kinetic analyses of each stabilizing effect permit selection of a rational combination of stabilizing methods for successful synergy in stabilizing nucleic acid assemblies.
Authors:
Hidetaka Torigoe; Atushi Maruyama; Satoshi Obika; Takeshi Imanishi; Takuma Katayama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemistry     Volume:  48     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-15     Completed Date:  2009-05-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3545-53     Citation Subset:  IM    
Affiliation:
Department of Applied Chemistry, Faculty of Science, Tokyo UniVersity of Science, 1-3 Kagurazaka,Shinjuku-ku, Tokyo 162-8601, Japan. htorigoe@rs.kagu.tus.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Base Pairing
DNA / chemistry*
Dextrans / chemistry*
Drug Synergism
Kinetics
Nucleic Acid Conformation*
Nucleic Acid Heteroduplexes / chemistry*
Oligonucleotides / chemistry*
Polylysine / analogs & derivatives*,  chemistry
Chemical
Reg. No./Substance:
0/Nucleic Acid Heteroduplexes; 0/Oligonucleotides; 0/locked nucleic acid; 0/poly(lysine)-graft-dextran; 0/triplex DNA; 25104-18-1/Polylysine; 9004-54-0/Dextrans; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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