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 (AcImPyiPrThDp) shows similar self-assembly characteristics to thiazotropsin A (FoPyPyiPrThDp), 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.