期刊
NUCLEIC ACIDS RESEARCH
卷 39, 期 1, 页码 325-336出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq723
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资金
- National Institutes of Health [RO1CA78754]
- Japan Society for the Promotion of Science
- NATIONAL CANCER INSTITUTE [R01CA078754] Funding Source: NIH RePORTER
The 1.7 angstrom X-ray crystal structure of the B-DNA dodecamer, [d(CGCGAATTCGCG)](2) (DDD)-bound non-covalently to a platinum(II) complex, [{Pt(NH3)(3)}(2)-mu-{trans-Pt(NH3)(2)(NH2(CH2)(6)NH2)(2)}](NO3)(6) (1, TriplatinNC-A,) shows the trinuclear cation extended along the phosphate backbone and bridging the minor groove. The square planar tetra-am(m)ine Pt(II) units form bidentate N-O-N complexes with OP atoms, in a Phosphate Clamp motif. The geometry is conserved and the interaction prefers O2P over O1P atoms (frequency of interaction is O2P > O1P, base and sugar oxygens > N). The binding mode is very similar to that reported for the DDD and [{trans-Pt(NH3)(2)(NH2(CH2)(6)(NH3+)}(2)-mu-trans-Pt(NH3)(2)(NH2(CH2)(6)NH2) (2)}](NO3)(8) (3, Triplatin NC), which exhibits in vivo anti-tumour activity. In the present case, only three sets of Phosphate Clamps were found because one of the three Pt(II) coordination spheres was not clearly observed and was characterized as a bare Pt2+ ion. Based on the electron density, the relative occupancy of DDD and the sum of three Pt(II) atoms in the DDD-1 complex was 1:1.69, whereas the ratio for DDD-2 was 1:2.85, almost the mixing ratio in the crystallization drop. The high repetition and geometric regularity of the motif suggests that it can be developed as a modular nucleic acid binding device with general utility.
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