The phosphate clamp: a small and independent motif for nucleic acid backbone recognition.
The 1.7 Å 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-µ-{trans-Pt(NH₃)₂(NH₂(CH₂)₆NH₂)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-µ-{trans-Pt(NH₃)₂(NH₂(CH₂)₆NH₂)₂}](NO₃)₈ (3, TriplatinNC), 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.
Komeda
Seiji
S
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
Moulaei
Tinoush
T
Chikuma
Masahiko
M
Odani
Akira
A
Kipping
Ralph
R
Farrell
Nicholas P
NP
Williams
Loren Dean
LD
D000970:Antineoplastic Agents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009944:Organoplatinum Compounds / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010710:Phosphates; D004247:DNA; D012964:Sodium