ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
O18. X-ray Crystallographic Studies on DNA Binding Modes of Polyaminebridged
Polynuclear Pt(II) Complexes
S. Komeda a , A. Odani b , M. Chikuma c , N. Farrell d , L. Williams e
a Department of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho,
513-0816, Suzuka, Japan
e-mail: komedas@suzuka-u.ac.jp
b School of Pharmaceutical Sciences, Kanazawa University, Kakuma-cho, 920-1192, Kanazawa, Japan
c Graduate School of Pharmaceuticak Sciences, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara,
569-1094, Takatsuki, Japan
d Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, 23284-2006, Richmond,
VA, United States
e School of Chemistry and Biochemistry, Georgia Institute of Technology, 30332-0400, Atlanta, GA, United
States
The extensive pre-associations of polyamine-bridged polynuclear Pt(II) complexes with DNA presumably arise
from the high positive charge (+2 ~ +8) and would be involved in the mechanism of their anticancer actions [1].
The results obtained from pre-association studies will allow us to estimate critical parameters in biological
mechanism [2].
Here we present three of X-ray crystal structures of a double-stranded B-DNA dodecamer,
[d(CGCGAATTCGCG)]2 (Deckerson-Drew dodecamer: DDD), each bound non-covalently to different
polynuclear platinum(II) complexes, [{cis-Pt(NH3)2(NH2(CH2)6NH3 + )}2-µ-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}] 8+
(AH78), [{Pt(NH3)3}2-µ-{trans-Pt
(NH3)2(NH2(CH2)6NH2)2}] 6+ (AH44) and [{Pt(NH3)3}2-µ-{NH2(CH2)3NH2 +
(CH2)4NH2 + (CH2)3NH2)}] 6+ (AH59). In the Pt-DDD crystal structures the phosphate backbone attracts the Pt
complexes by a DNA binding unit, we call "Phosphate Clamp". A Phosphate Clamp is a cyclic structure with
single OP, which accepts two hydrogen bonds, one from each of two am(m)ine ligands of a single Pt(II) center.
By two sets of Phosphate Clamps polynuclear Pt(II) complexes track the DNA backbone along the single strand
of the DDD or bridges two strands across the minor groove Implications of these findings are discussed.
References:
[1] Qu, Y.; Harris, A.; Hegmans, A.; Petz, A.; Kabolizadeh, P.; Penazova, H.; Farrell, N. J. Inorg. Biochem.
2004, 98, 1591-1598
[2] Komeda, S.; Moulaei, T.; Woods, K. K.; Chikuma, M.; Farrell N. P.; Williams, L. D. J. Am. Chem. Soc.
2006, 128, 16092-16103.
_____________________________________________________________________
105