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DNA recognition by intercalators and hybrid molecules
Author(s) -
Waring Michael J.,
Bailly Christian
Publication year - 1994
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.300070208
Subject(s) - footprinting , dna , guanosine , guanine , moiety , chemistry , stereochemistry , inosine , dna footprinting , intercalation (chemistry) , nucleotide , molecule , biochemistry , combinatorial chemistry , gene , adenosine , dna binding protein , base sequence , inorganic chemistry , organic chemistry , transcription factor
Experimental are described which probe the role of the 2‐amino group of guanine as a critical determinant of the recognition of nucleotide sequences in DNA by specific ligands. Homologous samples of tyr T DNA substituted with inosine or 26‐diaminopourine residues in place of guanosine or adenine respectively yield characteristically modified footprinting patterns when challenged with sequence‐selective antibiotics such as echinomycin, actinomycin or netrospin. The capacity of small molecules to recognise particular DNA sequences is exploited in the ‘combilexin’ strategy to target small molecules to defined sites in DNA. A composite molecule containing a distamycin moiety linked to an intercalating ellipticine derivative has been synthesised and shown to bind tightly to DNA but without much sequence‐selectivity. Refinement of this molecule based on predictions from molecular modelling has led to the synthesis of a second generation derivative bearing an additional positive charge: this new hybrid molecule is strongly selective for binding to AT‐rich tracts in DNA.