Linked Life Data

19170613

Source:http://linkedlifedata.com/resource/pubmed/id/19170613

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2009-4-15
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3545-53
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Synergistic stabilization of nucleic acid assembly by 2'-O,4'-C-methylene-bridged nucleic acid modification and additions of comb-type cationic copolymers.
pubmed: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
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't