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existence of different conformations, and in the most favourable cases have also
allowed the full characterization of their stereochemistry. Moreover, several inter-
ligand interactions, some of which had remained unrecognized for a long time, have
been revealed and a hierarchy among them has been established.
Our analysis, based on solution results with adducts containing specially
designed carrier ligands, has allowed us to rationalize computational, solution-state,
and solid-state results on
cis
- (NH
3
)
2
Pt crosslink adducts in a more consistent manner
than previous interpretations based on the
cis
- (NH
3
)
2
Pt adducts themselves. This
success verifi es the value of the retro modelling approach. In addition, by using retro
models we found dramatic differences in the relative stability of different forms of
oligonucleotides (coil, hairpin and duplex) dependent on the carrier ligand.
We believe that in the future the use of retro models for the stabilization of
single conformers and the characterization of their stereochemistry will play an
important role in the interpretation of experimental data pertaining to dynamic
systems and in the validation of results coming from theoretical investigations.
Acknowledgements
G. Natile gratefully acknowledges the collaboration with Prof. Dr L. G. Marzilli
(Louisiana State University) which, over a period of nearly two decades, has led to
the major discoveries presented in this article. Thanks are also due to the many
students and postdoctoral researchers who have contributed and whose names are
listed in the references as coauthors of previous papers. Support and sponsorship
from European COST Actions D39/0004/06 'Structure, recognition, and processing
of DNA damage by antitumour metal-based compounds', the Italian Ministry for
University and Research (MUR, Rome), the University of Bari and the Interuni-
versity Consortium for Research in the Chemistry of Metal Ions in Biological
Systems (C.I.R.C.M.S.B.) are also acknowledged.
References
1.
Drobnik , J. ; Antitumour activity of platinum complexes ;
Cancer Chemother. Pharmacol.
,
1983 ,
10
( 3 ), 145 - 149 .
Pil , P. ; Lippard , S. ; Cisplatin and related drugs . In
Encyclopedia of Cancer
; Bertino , J.R. ,
Ed., Academic Press , San Diego , 1997 , 392 - 410 .
Bierbach , U. ; Qu , Y. ; Hambley , T.W. ; Peroutka , J. ; Nguyen , H.L. ;
2.
3.
Doedee , M. ; Farrell , N. ;
Synthesis, structure, biological activity, and DNA binding of platinum(II) complexes of
the type
trans
- PtCl
2
(NH
3
)L (L = planar nitrogen base). Effect of L and
cis/trans
isomer-
ism on sequence specifi city and unwinding properties observed in globally platinated
DNA ;
Inorg. Chem.
, 1999 ,
38
, 3535 - 3542 .
Di Blasi , P. ; Bernareggi , A. ; Beggiolin , G. ; Piazzoni , L. ; Menta , E. ; Formento , M. ; Cyto-
toxicity, cellular uptake and DNA binding of the novel trinuclear platinun complex BBR
3464 in sensitive and cisplatin resistant murine leukemia cells;
Anticancer Res.
, 1998 ,
18
,
3113 - 3117 .
4.
