|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 50, 48076-48086, December 13, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the The novel phase II antitumor polynuclear platinum
drug BBR3464
([(trans-PtCl(NH3)2)2(µ-trans-Pt(NH3)2(NH2(CH2)6NH2)2)](NO3)4) forms intra- and interstrand cross-links (CLs) on DNA (which is the
pharmacological target of platinum drugs). We examined first in
our recent work how various intrastrand CLs of BBR3464 affect the
conformation of DNA and its recognition by cellular
components (Zehnulova, J., Kasparkova, J., Farrell, N., and Brabec, V. (2001) J. Biol. Chem. 276, 22191-22199). In the
present work, we have extended the studies on the DNA interstrand CLs
of this drug. The results have revealed that the interstrand CLs are
preferentially formed between guanine residues separated by 2 base
pairs in both the 3'
DNA Interstrand Cross-links of the Novel Antitumor Trinuclear
Platinum Complex BBR3464
CONFORMATION, RECOGNITION BY HIGH MOBILITY GROUP DOMAIN
PROTEINS, AND NUCLEOTIDE EXCISION REPAIR*
§,,
, and**
Institute of Biophysics, Academy of Sciences
of the Czech Republic, Kralovopolska 135, CZ-61265 Brno, Czech
Republic and the ¶ Department of Chemistry, Virginia Commonwealth
University, Richmond, Virginia 23284-2006
3' and 5' 5' directions. The major
1,4-interstrand CLs distort DNA, inducing a directional bending of the
helix axis and local unwinding of the duplex. Although such distortions
represent a potential structural motif for recognition by high mobility group proteins, these proteins do not recognize 1,4-interstrand CLs of
BBR3464. On the other hand, in contrast to intrastrand adducts of
BBR3464, 1,4-interstrand CLs are not removed from DNA by nucleotide
excision repair. It has been suggested that interstrand CLs of BBR3464
could persist considerably longer in cells compared with intrastrand
adducts, which would potentiate the toxicity of the interstrand lesions
to tumors sensitive to this polynuclear drug.
*
This work was supported by Grant 305/02/1552A from the Grant
Agency of the Czech Republic, by Grant A5004101 from the Grant Agency
of the Academy of Sciences of the Czech Republic, by Grant NL6058-3/2000 from the Internal Grant Agency of the Ministry of Health
of the Czech Republic, and by the Wellcome Trust, United Kingdom (to
J. K. and V. B.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence may be addressed. Tel.: 804-828-6320;
Fax: 804-828-8599; E-mail: nfarrell@mail1.vcu.edu.
**
To whom correspondence may be addressed. Tel.: 420-5-4151-7148;
Fax: 420-5-4124-0499; E-mail: brabec@ibp.cz.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Billecke, S. Finniss, L. Tahash, C. Miller, T. Mikkelsen, N. P. Farrell, and O. Bogler Polynuclear platinum anticancer drugs are more potent than cisplatin and induce cell cycle arrest in glioma Neuro-oncol, July 1, 2006; 8(3): 215 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Billecke, I. Malik, A. Movsisyan, S. Sulghani, A. Sharif, T. Mikkelsen, N. P. Farrell, and O. Bogler Analysis of Glioma Cell Platinum Response by Metacomparison of Two-dimensional Chromatographic Proteome Profiles Mol. Cell. Proteomics, January 1, 2006; 5(1): 35 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kasparkova, M. Fojta, N. Farrell, and V. Brabec Differential recognition by the tumor suppressor protein p53 of DNA modified by the novel antitumor trinuclear platinum drug BBR3464 and cisplatin Nucleic Acids Res., October 14, 2004; 32(18): 5546 - 5552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kasparkova, O. Novakova, V. Marini, Y. Najajreh, D. Gibson, J.-M. Perez, and V. Brabec Activation of Trans Geometry in Bifunctional Mononuclear Platinum Complexes by a Piperidine Ligand: MECHANISTIC STUDIES ON ANTITUMOR ACTION J. Biol. Chem., November 28, 2003; 278(48): 47516 - 47525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Novakova, J. Kasparkova, J. Malina, G. Natile, and V. Brabec DNA-protein cross-linking by trans-[PtCl2(E-iminoether)2]. A concept for activation of the trans geometry in platinum antitumor complexes Nucleic Acids Res., November 15, 2003; 31(22): 6450 - 6460. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |