The phosphate clamp: a small and independent motif for nucleic acid backbone recognition.

The phosphate clamp: a small and independent motif for nucleic acid backbone recognition.
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DOI:
10.1093/nar/gkq723
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发表时间:
2011-01
影响因子:
14.9
通讯作者:
Williams LD
Williams LD
中科院分区:
生物学2区
文献类型:
--
作者:
Komeda S;Moulaei T;Chikuma M;Odani A;Kipping R;Farrell NP;Williams LD

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B-DNA十二聚体,[d(CGCGAATTCGCG)]2(DDD)-与铂(II)络合物[{Pt(NH3)3}2-µ-{trans-Pt(NH3)2(NH 2(CH 2)6 NH 2)2}](NO3)6(1,TriplatinNC-A,)非共价结合的1.7 X射线晶体结构显示三核阳离子沿磷酸骨架沿着延伸并桥接小沟。正方形平面四胺Pt(II)单元与OP原子形成双齿N-O-N络合物,以磷酸盐钳基序。几何结构是保守的,相互作用更倾向于O2 P而不是O 1 P原子(相互作用的频率为O2 P> O 1 P,碱基和糖氧> N)。结合模式与DDD和[{trans-Pt(NH3)2(NH 2(CH 2)6(NH3+)}2-µ-{trans-Pt(NH3)2(NH 2(CH 2)6 NH 2)2}](NO3)8(3,TriplatinNC)报告的结合模式非常相似,其表现出体内抗肿瘤活性。在目前的情况下,只发现了三组磷酸盐夹,因为三个Pt(II)配位球中的一个没有被清楚地观察到,并且被表征为裸露的Pt 2+离子。基于电子密度,DDD和三个Pt(II)原子的总和在DDD-1络合物中的相对占有率为1:1.69,而DDD-2的比例为1:2.85,几乎是结晶液滴中的混合比例。基序的高度重复性和几何规则性表明它可以被开发为具有通用性的模块化核酸结合装置。
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.
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