Crystal Structure of Δ-[Ru(bpy)₂dppz]²⁺ Bound to Mismatched DNA Reveals Side-by-side Metalloinsertion and Intercalation

Overview

Journal Nat Chem

Specialty Chemistry

Date 2012 Jul 25

PMID 22824892

Citations 73

Authors

Hang Song

Jens T Kaiser

Jacqueline K Barton

Affiliations

Soon will be listed here.

Abstract

DNA mismatches represent a novel target in the development of diagnostics and therapeutics for cancer, because deficiencies in DNA mismatch repair are implicated in cancers, and cells that are repair-deficient show a high frequency of mismatches. Metal complexes with bulky intercalating ligands serve as probes for DNA mismatches. Here, we report the high-resolution (0.92 Å) crystal structure of the ruthenium 'light switch' complex Δ-[Ru(bpy)(2)dppz](2+) (bpy = 2,2'-bipyridine and dppz = dipyridophenazine), which is known to show luminescence on binding to duplex DNA, bound to both mismatched and well-matched sites in the oligonucleotide 5'-(dCGGAAATTACCG)(2)-3' (underline denotes AA mismatches). Two crystallographically independent views reveal that the complex binds mismatches through metalloinsertion, ejecting both mispaired adenosines. Additional ruthenium complexes are intercalated at well-matched sites, creating an array of complexes in the minor groove stabilized by stacking interactions between bpy ligands and extruded adenosines. This structure attests to the generality of metalloinsertion and metallointercalation as DNA binding modes.

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