Linkage Structures Strongly Influence the Binding Cooperativity of DNA Intercalators Conjugated to Triplex Forming Oligonucleotides

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 1994 Feb 11

PMID 8127688

Citations 8

Authors

F M Orson

B M Kinsey

W M McShan

Affiliations

Soon will be listed here.

Abstract

Conjugation of DNA intercalators to triple helix forming oligodeoxynucleotides (ODN's) can enhance ODN binding properties and consequently their potential ability to modulate gene expression. To test the hypothesis that linkage structure could strongly influence the binding enhancement of intercalator conjugation with triplex forming ODN's, we have used a model system to investigate binding avidity of short oligomers conjugated to DNA intercalators through various linkages. Using a dA10.T10 target sequence imbedded in a 20 bp duplex, binding avidities of a T10 ODN joined to the DNA intercalator 6,9-diamino, 3-methoxy acridine (DAMA) by 8 different 5' linkages were measured using an electrophoretic mobility shift assay. Although unmodified T10 has a very limited capacity for stable binding under these conditions (apparent Kd > 250 microM at 4 degrees C), conjugation to DAMA using flexible linkers of certain lengths and chemical compositions greatly enhanced binding (Kd of 1 microM at 4 degrees C). Other linkers, however, modestly enhanced binding or had no effect on binding at all. Thus, the length, flexibility, and chemical composition of linker structures all substantially influence intercalator conjugated oligodeoxynucleotide binding avidity.

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