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Recognition of the DNA Minor Groove by Thiazotropsin Analogues
Author(s) -
Alniss Hasan Y.,
Salvia MarieVirginie,
Sadikov Mykhailo,
Golovchenko Igor,
Anthony Nahoum G.,
Khalaf Abedawn I.,
MacKay Simon P.,
Suckling Colin J.,
Parkinson John A.
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402202
Subject(s) - dna , chemistry , stereochemistry , minor groove , molecule , formamide , nucleobase , context (archaeology) , base pair , crystallography , biochemistry , biology , organic chemistry , paleontology
Solution‐phase self‐association characteristics and DNA molecular‐recognition properties are reported for three close analogues of minor‐groove‐binding ligands from the thiazotropsin class of lexitropsin molecules; they incorporate isopropyl thiazole as a lipophilic building block. Thiazotropsin B (AcImPy i Pr ThDp) shows similar self‐assembly characteristics to thiazotropsin A (FoPyPy i Pr ThDp), although it is engineered, by incorporation of imidazole in place of N ‐methyl pyrrole, to swap its DNA recognition target from 5′‐AC TA GT‐3′ to 5′‐AC GC GT‐3′. Replacement of the formamide head group in thiazotropsin A by nicotinamide in AIK‐18/51 results in a measureable difference in solution‐phase self‐assembly character and substantially enhanced DNA association characteristics. The structures and associated thermodynamic parameters of self‐assembled ligand aggregates and their complexes with their respective DNA targets are considered in the context of cluster targeting of DNA by minor‐groove complexes.