Photosensitive metal complexes that are able to bind to DNA duplexes hold promise for diagnostic and therapeutic applications — but the precise details of how they interact with DNA need to be better understood. A collection of articles in this focus highlight some of the latest advances in elucidating their binding modes as well as challenges associated with this area of research.
doi:10.1038/nchem.1423
Structure by structure, more information is steadily being gathered on how small molecules bind to DNA. A better understanding of the interactions involved in such processes will be crucial for the successful design of compounds for specific diagnostic and therapeutic purposes.
Full Text - Double-helix disruption | PDF (192 KB) - Double-helix disruption
Subject terms: Biochemistry | Inorganic chemistry
Interview with Claudia Turro
doi:10.1038/nchem.1420
Claudia Turro from The Ohio State University talks Nature Chemistry through the different binding modes small metal complexes can adopt when interacting with DNA — and why elucidating them in detail matters.
Full Text - Binding manners | PDF (268 KB) - Binding manners
Stephen Neidle
doi:10.1038/nchem.1413
The interactions between ruthenium complexes and DNA duplexes, elucidated in detail in three different crystal structures, have been found to occur through the minor groove — an unexpected binding mode, but perhaps not such a strange one.
Full Text - Interactions with DNAInto the minor groove | PDF (294 KB) - Interactions with DNAInto the minor groove
Subject terms: Biochemistry | Inorganic chemistry
See also: Article by Song et al. | Article by Niyazi et al.
Hang Song, Jens T. Kaiser & Jacqueline K. Barton
doi:10.1038/nchem.1375
A ‘light switch’ ruthenium complex is known to show enhanced luminescence in the presence of DNA mismatches — emerging targets for cancer diagnostics and therapeutics — but the way it interacts with DNA has remained unclear. Now, metalloinsertion into and metallointercalation at the minor groove of the double helix have been unambiguously observed in a high-resolution crystal structure.
Abstract - Crystal structure of ?-[Ru(bpy)2dppz]2+ bound to mismatched DNA reveals side-by-side metalloinsertion and intercalation | Full Text - Crystal structure of ?-[Ru(bpy)2dppz]2+ bound to mismatched DNA reveals side-by-side metalloinsertion and intercalation | PDF (3,592 KB) - Crystal structure of ?-[Ru(bpy)2dppz]2+ bound to mismatched DNA reveals side-by-side metalloinsertion and intercalation | Supplementary information | Chemical compounds
Subject terms: Biochemistry | Inorganic chemistry
See also: News and Views by Neidle
Hakan Niyazi, James P. Hall, Kyra O'Sullivan, Graeme Winter, Thomas Sorensen, John M. Kelly & Christine J. Cardin
doi:10.1038/nchem.1397
Elucidating how small molecules bind to DNA is crucial to bio-sensing and therapy applications. Two crystal structures now show the binding modes of a ‘light switch’ ruthenium complex — whose luminescence in solution increases in the presence of DNA — with oligonucleotide duplexes containing either TA/TA or AT/AT central steps, revealing a specific intercalation mode with the TA/TA species.
Abstract - Crystal structures of ?-[Ru(phen)2dppz]2+ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes | Full Text - Crystal structures of ?-[Ru(phen)2dppz]2+ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes | PDF (7,788 KB) - Crystal structures of ?-[Ru(phen)2dppz]2+ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes | Supplementary information | Chemical compounds
Subject terms: Biochemistry | Inorganic chemistry
See also: News and Views by Neidle
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