Sequence-specific recognition of DNA by organic small molecules offers a potentially general approach for the regulation of gene expression. It is necessary to develop a new class of compounds that can be rationally designed from the established modules which can bind strongly and selectively with specific DNA sequences. In this work we have designed a library of novel heterocyclic cations which can selectively bind with mixed-base-pair DNA sequences. Evidence of strong interaction of the compounds with a GC base pair (bp) adjacent to two AT rich sites has been obtained from thermal denaturation, circular dichroism, biosensor-surface plasmon resonance, isothermal calorimetric and mass spectrometry studies. Some of our new compounds bind to the target sequence with sub-nanomolar binding constants with very slow dissociation kinetics and very high selectivity over the related sequences without the GC base pair. By this approach we have introduced a new way to recognize more complex DNA sequences by synthetic organic molecules. The molecular modeling studies also provide the structure-sequence relationship between ligand-DNA complexes. (supported by NIH AI064200)

Novel heterocyclic minor groove binding compounds for targeting mixed-base-pair DNA sequences

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.