TERNARY PT(II)-AMINO-ACID-NUCLEOTIDE COMPLEXES - KINETICS OF FORMATION

TERNARY PT(II)-AMINO-ACID-NUCLEOTIDE COMPLEXES - KINETICS OF FORMATION
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DOI:
10.1016/0020-1693(94)03797-3
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发表时间:
1994-04-01
影响因子:
2.8
通讯作者:
BERMAN, HM
BERMAN, HM
中科院分区:
化学3区
文献类型:
--
作者:
GIBSON, D;ARVANITIS, GM;BERMAN, HM

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以Pt(II)与核苷酸5′-GMP、3′-GMP和5′-dGMP (GMP =鸟苷膦)以及与氨基酸N(α)- boc - l -组氨酸、N(α)- boc - l -蛋氨酸和1-甲基咪唑(1-MeIm)的三元配合物为模型,研究了Pt介导的dna -蛋白交联。三胺配合物[PtAm2(L)Cl]+(其中Am2=顺式或反式(NH)2或乙二胺,L=1-MeIm或N(α)- boc -L-his- n3)容易与单核苷酸5'- gmp, 3'- gmp和5'- dgmp反应形成三元交联配合物PtAm2(L)(核苷酸)。5‘核苷酸比3’核苷酸对三胺复合物的反应更快。H-1 NMR动力学研究表明,顺式-[PtAm2(1-MeIm-N3)C]]+与5′- gmp的反应速度快于反式异构体(二级速率常数k2分别为0.756和0.358 M-1 s-1),乙二胺配合物的反应速度快于这两种异构体(k2=1.09 M-1 s-1)。
Ternary complexes of Pt(II) with the nucleotides 5'-GMP, 3'-GMP and 5'-dGMP (GMP = guanosinemonophosphate), and with the amino acids N(alpha)-BOC-L-histidine, N(alpha)-BOC-L-methionine and 1-methylimidazole (1-MeIm) were studied as models for Pt mediated DNA-protein crosslinks. The triamine complexes [PtAm2(L)Cl]+ (where Am2=cis- or trans-(NH)2 or ethylenediamine and L=1-MeIm or N(alpha)-BOC-L-his-N3) react readily with the mononucleotides 5'-GMP, 3'-GMP and 5'-dGMP to form the ternary crosslinked complexes PtAm2(L)(nucleotide). The 5'-nucleotides react faster than their 3' counterparts towards either triamine complex. Kinetic studies by H-1 NMR show that cis-[PtAm2(1-MeIm-N3)C]]+ reacts with 5'-GMP faster than the trans isomer (second order rate constants k2=0.756 and 0.358 M-1 s-1, respectively) and that the ethylenediamine complex is faster than both (k2=1.09 M-1 S-1).