4QIO

Lambda-[Ru(TAP)2(dppz)]2+ bound to d(TCGGCGCCIA) at high resolution

Summary for 4QIO

• Entry DOI: 10.2210/pdb4qio/pdb
• Related: 3QRN
• Descriptor: 5'-D(*TP*CP*GP*GP*CP*GP*CP*CP*IP*A)-3', BARIUM ION, Ru(tap)2(dppz) complex, ... (5 entities in total)
• Functional Keywords: intercalation, ruthenium complex, inosine, dna
• Total number of polymer chains: 1
• Total formula weight: 3951.49

Authors

Gurung, S.P.,Hall, J.P.,Cardin, C.J. (deposition date: 2014-06-01, release date: 2015-06-03, Last modification date: 2024-02-28)

Primary citation

Keane, P.M.,Hall, J.P.,Poynton, F.E.,Poulsen, B.C.,Gurung, S.P.,Clark, I.P.,Sazanovich, I.V.,Towrie, M.,Gunnlaugsson, T.,Quinn, S.J.,Cardin, C.J.,Kelly, J.M.
Inosine Can Increase DNA's Susceptibility to Photo-oxidation by a Ru II Complex due to Structural Change in the Minor Groove.
Chemistry, 23:10344-10351, 2017

PubMed Abstract: Key to the development of DNA-targeting phototherapeutic drugs is determining the interplay between the photoactivity of the drug and its binding preference for a target sequence. For the photo-oxidising lambda-[Ru(TAP) (dppz)] (Λ-1) (dppz=dipyridophenazine) complex bound to either d{T C G G C G C C G A } (G9) or d{TCGGCGCCIA} (I9), the X-ray crystal structures show the dppz intercalated at the terminal T C ;G A step or T C ;I A step. Thus substitution of the G nucleobase by inosine does not affect intercalation in the solid state although with I9 the dppz is more deeply inserted. In solution it is found that the extent of guanine photo-oxidation, and the rate of back electron-transfer, as determined by pico- and nanosecond time-resolved infrared and transient visible absorption spectroscopy, is enhanced in I9, despite it containing the less oxidisable inosine. This is attributed to the nature of the binding in the minor groove due to the absence of an NH group. Similar behaviour and the same binding site in the crystal are found for d{TTGGCGCCAA} (A9). In solution, we propose that intercalation occurs at the C G ;C I or T G ;C A steps, respectively, with G the likely target for photo-oxidation. This demonstrates how changes in the minor groove (in this case removal of an NH group) can facilitate binding of Ru dppz complexes and hence influence any sensitised reactions occurring at these sites. No similar enhancement of photooxidation on binding to I9 is found for the delta enantiomer.

PubMed: 28543779
DOI: 10.1002/chem.201701447

Experimental method

X-RAY DIFFRACTION (0.95 Å)