Compound Shape Effects in Minor Groove Binding Affinity and Specificity for Mixed Sequence DNA.

ABSTRACT: AT specific heterocyclic cations that bind in the DNA duplex minor groove have had major successes as cell and nuclear stains and as therapeutic agents which can effectively enter human cells. Expanding the DNA sequence recognition capability of the minor groove compounds could also expand their therapeutic targets and have an impact in many areas, such as modulation of transcription factor biological activity. Success in the design of mixed sequence binding compounds has been achieved with N-methylbenzimidazole ( N-MeBI) thiophenes which are preorganized to fit the shape of the DNA minor groove and H-bond to the -NH of G·C base pairs that project into the minor groove. Initial compounds bind strongly to a single G·C base pair in an AT context with a specificity ratio of 50 ( K_D

SUBMITTER: Guo P 

PROVIDER: S-EPMC6399738 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature