Dinuclear platinum complexes containing planar aromatic ligands to enhance stacking interactions with proteins.
Dinuclear platinum complexes containing planar aromatic ligands to enhance stacking interactions with proteins.
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DOI：
10.1002/cmdc.201402052
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发表时间：
2014-06
期刊：
影响因子：
3.4
通讯作者：
Farrell, Nicholas P.
中科院分区：
文献类型：
--
作者：
Ma, Erin S. F.;Daniel, A. Gerard;Farrell, Nicholas P.
为了设计对π-π叠加和与目标生物分子的静电相互作用具有更高亲和力的药物，合成了[{顺式- pt (A)2(L)}2-μ-{反式-1,4-dach}](NO3)4 ((A)2 = （NH3)2或乙二胺（en）， L =喹啉（quin）或苯并噻唑（bztz）， dach =反式-1,4-二氨基环己烷）的配合物。由前体K[PtCl3(quin)](1)合成喹啉配合物[{顺式- pt (en)(quin)}2-μ-(dach)](NO3)4(9)，苯并噻唑配合物[{顺式- pt (A)2(bztz)}2-μ-(dach)](NO3)4 ((A)2 = (NH3)2 (10)；（A)2 = en(11)）由前体顺式-[Pt(A)2Cl(bztz)] ((A)2 = (NH3)2(7))合成；（A)2 = en (8)）荧光光谱法检测了它们与n -乙酰色氨酸和基于p53-mdm2 （FLASW）五肽识别序列的模型五肽（N-AcWLASW-OH）的相互作用。发现双核配合物比单核Pt类似物具有更强的荧光猝灭作用。分子模型表明了一种“三明治”结合模式，双核基序的灵活性可以设计出更具选择性和更强的结合复合物。在此基础上，制备了以嘌呤- 9-乙基鸟嘌呤（9-EtG）为堆叠基团的[{Pt(en)(9- etga)}2μ-H2N(CH2)6NH2]4+，对A2780和OsACL肿瘤细胞具有良好的细胞毒性。
In an approach to design drugs with higher affinity for π-π stacking and electrostatic interactions with targeted biomolecules, complexes of the type [{cis-Pt(A)2(L)}2-μ-{trans-1,4-dach}](NO3)4 ((A)2 = (NH3)2 or ethylenediamine (en), L = quinoline (quin) or benzothiazole (bztz), dach = trans-1,4-diaminocyclohexane) were synthesized. The quinoline complex, [{cis-Pt(en)(quin)}2-μ-(dach)](NO3)4 (9) was synthesized from the precursor K[PtCl3(quin)] (1) while the benzothiazole complexes, [{cis-Pt(A)2(bztz)}2-μ-(dach)](NO3)4 ((A)2 = (NH3)2 (10); (A)2 = en (11)) were synthesized from the precursors cis-[Pt(A)2Cl(bztz)] ((A)2 = (NH3)2 (7); (A)2 = en (8)). Their interactions with N-acetyltryptophan and a model pentapeptide (N-AcWLASW-OH) modeled on the pentapeptide recognition sequence of p53-mdm2 (FLASW) were examined by fluorescence spectroscopy. The dinuclear complexes were found to be significantly stronger quenchers of fluorescence than their mononuclear Pt analogs. Molecular modeling suggests a “sandwich” mode of binding and the flexibility of the dinculear motif can allow design for more selective and stronger-binding complexes. Based on these results a further prototype, [{Pt(en)(9-EtGua)}2μ-H2N(CH2)6NH2]4+, incorporating the purine 9-Ethylguanine (9-EtG) as a stacking moiety was prepared which showed good cytotoxicity in A2780 and OsACL tumor cell lines.
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影响因子：
4.6
作者：
Anzellotti, AI;Ma, ES;Farrell, N
通讯作者：
Farrell, N
DOI：
10.1002/9780470132630.ch23
发表时间：
1998-01-01
期刊：
INORGANIC SYNTHESES, VOL 32
影响因子：
--
作者：
Kukushkin, VY;Oskarsson, A;Lippard, SJ
通讯作者：
Lippard, SJ
影响因子：
14.9
作者：
Komeda S;Moulaei T;Chikuma M;Odani A;Kipping R;Farrell NP;Williams LD
通讯作者：
Williams LD
影响因子：
--
作者：
Dong, YB;Yang, HL;McMasters, KM
通讯作者：
McMasters, KM
影响因子：
2.8
作者：
GIBSON, D;ARVANITIS, GM;BERMAN, HM
通讯作者：
BERMAN, HM