当前位置： SCI文献检索 > JOURNAL OF INORGANIC BIOCHEMISTRY期刊下所有文献 > Comparison of structural effects in 1,4 DNA-DNA interstrand cross-links formed by dinuclear and trinuclear platinum complexes.

Comparison of structural effects in 1,4 DNA-DNA interstrand cross-links formed by dinuclear and trinuclear platinum complexes.

Abstract：

:The novel anticancer drug ([[trans-PtCl(NH(3))(2)](2)-mu-[trans-Pt(NH(3))(2)(NH(2)(CH(2))(6)NH(2))(2)]](NO(3))(4)) (BBR3464, 1,0,1/t,t,t, TPC) forms a 1,4-interstrand cross-linked adduct with the self-complementary DNA octamer 5'-d(ATG*TACAT)(2)-3', with the two platinum atoms coordinated in the major groove at N7 positions of guanines four base pairs apart on opposite DNA strands [Y. Qu, N.J. Scarsdale, M.-C. Tran, N. Farrell, J. Biol. Inorg. Chem. 8 (2003) 19-28]. The structure of the identical cross-link formed by the dinuclear [[trans-PtCl(NH(3))(2)](2)-mu-NH(2)(CH(2))(6)NH(2)]](NO(3))(2) (BBR3005, 1,1/t,t, DPC) was examined for comparison. The adduct was characterized and analyzed by MS, UV and NMR spectroscopy. NMR analysis of the adduct shows platination of the unique guanine residues. The strong H8/H1' intraresidue cross-peaks observed for all purine residues (A1, G3, A5 and A7) are consistent with a syn-conformation of the nucleoside unit in all cases. Thus, the structure resembles closely that formed by the trinuclear compound. Further confirmation of this similarity comes from the increase in melting temperature (66 degrees for DPC, 60 degrees for TPC, 22 degrees for free oligonucleotide). Since DNA is the principal target in vivo for these Pt cross-linking agents, the unique structural perturbations induced by these cross-links may be related to the increased cytotoxicity and antitumor activity of polynuclear platinum compounds as compared to cisplatin (cis-DDP). The similarity in the structures suggests opportunities to "deliver" the cross-link in a more efficient manner than the current clinically tested drug.

journal_name

J Inorg Biochem

journal_title

Journal of inorganic biochemistry

authors

Qu Y,Scarsdale NJ,Tran MC,Farrell N

doi

10.1016/j.jinorgbio.2004.07.011

subject

Has Abstract

pub_date

2004-10-01 00:00:00

pages

1585-90

issue

10

eissn

0162-0134

issn

1873-3344

pii

S0162-0134(04)00204-1

journal_volume

98

pub_type

杂志文章

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