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Name (Title):
Antonio S. Torralba (NIMS postdoctoral fellow)
Affiliation:
ICYS, National Institute for Materials Science
Address:
1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan
Email: TORRALBA.Antonio@nims.go.jp
Home Page:
Presentation Title:
Ruthenium complexes for artificial endonucleases: DFT analysis of ligands and potential binding
interactions with DNA
Abstract:
Restriction endonucleases are enzymes that are able to cut DNA in a reparable way at welldefined
sequences. As such, they are important tools in genetic and metabolic engineering.
Unfortunately, naturally-occurring enzymes recognize a limited range of sequences and it is
almost impossible to customize them. A possible alternative to protein-based endonucleases is to
use ruthenium complexes, some of which are known to cleave DNA in the presence of light,
usually by oxidation of a nucleobase. Sequence specificity can potentially be achieved by
tethering short oligonucleotides to the metallic complex. However, these organometallic systems
are not free of problems. One of them is that the oxidative pathway which the reaction follows
makes recovery of the original, re-ligated DNA difficult.
A new kind of complex has been found (see Fig. 1), which is able to cut DNA following a
hydrolytic pathway, similar to that of natural enzymes [1]. This is a very promising system.
However, the details of the mechanism are not
understood. In particular, hydrogen-bonding seems
to be important, but the structure of the network is
not known. In addition, ligand functionalization is
key to reactivity. We use DFT, as implemented in
our linear-scaling code Conquest [2], to gain insight
into the reaction. As a first step, this contribution
presents electron-density calculations of elementary
Ru-complex ligands, notably bipyridines (bpy)
substituted by electron-donating and electronwithdrawing
groups, as well as glycouril.
Population analysis of the densities, along with
preliminary docking of the glycouril complex into
B-DNA, aimed at identifying binding sites, will
also be discussed.
Poster Session PIR-10
Fig. 1: Ruthenium bisbpy,bpyglycouril:
a complex able to hydrolyze DNA
References:
[1] M.S. Deshpande, A.A. Kumbhar and A.S. Kumbhar Inorg. Chem. (2007) 46, 5450-5452
[2] D. Bowler, R. Choudhury, M. Gillan and T. Miyazaki Phys. Stat. Sol. B (2006) 243, 989-
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