Single GC base pair recognition by a heterocyclic diamidine: structures, affinities, and dynamics

RSC Adv. 2024 Sep 18;14(40):29675-29682. doi: 10.1039/d4ra05957c. eCollection 2024 Sep 12.

Abstract

The recognition of specific genomic arrangements by rationally designed small molecules is fundamental for the expansion of targeted gene expression. Here, we report the first X-ray crystal structures that demonstrate single G (guanine) recognition by a highly selective diamidine (DB2447) in a mixed DNA sequence. The study presents detailed structural information on the mechanism of single G recognition by D2447 and its various interactions in the DNA minor groove. Molecular dynamics and binding studies were used to evaluate the details of our reported structures. The study provides structural insight and resources necessary for understanding single G selection in genomic sequences.