title: Targeting DNA Mismatches with Rhodium Metalloinsertors.
abstract: DNA has been exploited as a biological target of chemotherapeutics since the 1940s. Traditional chemotherapeutics, such as cisplatin and DNA-alkylating agents, rely primarily on increased uptake by rapidly proliferating cancer cells for therapeutic effects, but this strategy can result in off-target toxicity in healthy tissue. Recently, research interests have shifted towards targeted chemotherapeutics, in which a drug targets a specific biological signature of cancer, resulting in selective toxicity towards cancerous cells. Here, we review a family of complexes, termed rhodium metalloinsertors, that selectively target DNA base pair mismatches, a hallmark of mismatch-repair (MMR) deficient cancers. These rhodium metalloinsertors, bind DNA mismatches with high specificity and display high selectively in killing MMR-deficient versus MMR-proficient cells. This cell selectivity is unique for small molecules that bind DNA. Current generations of rhodium metalloinsertors have shown nanomolar potency along with high selectivity towards MMR-deficient cells, and show promise as a foundation for a new family of chemotherapeutics for MMR-deficient cancers.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena CA 91125.
authors.forename: Kelsey M
authors.initials: KM
authors.lastname: Boyle
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena CA 91125.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Barton
keywords: DNA Probe; Metalloinsertor; Mismatch Repair; Rhodium