Recognition of the DNA Minor Groove by Thiazotropsin Analogues.

Chembiochem : a European journal of chemical biology

PubMedID: 25045155

Alniss HY, Salvia MV, Sadikov M, Golovchenko I, Anthony NG, Khalaf AI, MacKay SP, Suckling CJ, Parkinson JA. Recognition of the DNA Minor Groove by Thiazotropsin Analogues. Chembiochem. 2014;.
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(iPr) ThDp) shows similar self-assembly characteristics to thiazotropsin A (FoPyPy(iPr) ThDp), although it is engineered, by incorporation of imidazole in place of N-methyl pyrrole, to swap its DNA recognition target from 5'-ACTAGT-3' to 5'-ACGCGT-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.