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Nucleic Acids Research, 1983, Vol. 11, No. 18 6571-6586
© 1983

CHEMISTRY

Similar binding of the carcinostatic drugs cis-[Pt[NH3)2] and [Ru(NH3)5Cl] Cl2 to tRNAphe and a comparison with the binding of the inactive trans-[Pt(NH3)2Cl2] complex - reluctance in binding to Watson-Crick base pain within doable helix

John R. Rubin, Michal Sabat* and Muttaiya Sundaralingam

Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison Madison, WI 53706, USA

*To whom correspondence should be addressed.

Received May 6, 1983. Revised August 22, 1983. Accepted August 22, 1983.

A comparative study of the binding of square planar cis- and trans-[Pt(NH3)2Cl2] complexes and the octahedral [Ru(NH3)5(H2O)]3+ complex to tRNAphe from yeast was carried out by X-ray crystallography. Both of the carcinostatic compounds, cis-[Pt(NH3)2Cl2] and [Ru(NH3)5(H2O)]3+ show similarities in their node of binding to tRNA. These complexes bind specifically to the N(7) positions of guanines G15 and G18 in the dihydrouridine loop. [Ru(NH3)5(H2O)]3+ has an additional binding site at N(7) of residue Gl after extensive soaking times (58 days). A noncovalent binding site for ruthenium is also observed in the deep groove of the acceptor stem helix with shorter (25 days) soaking time. The major binding site for the inactive trans-[Pt(NH3)Cl2] complex is at the N(1) positions of residues A73, with minor trans-Pt binding sites at the N(7) positions of residues Gm34, G18 and G43. The similarities in the binding modes of cis-[Pt(NH3)2Cl2] and [Ru(NH3)5(H2O)]3+ are expected to be related to their carcinostatic properties.


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S. Sherman, D Gibson, A. Wang, and S. Lippard
X-ray structure of the major adduct of the anticancer drug cisplatin with DNA: cis-[Pt(NH3)2(d(pGpG))]
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[Abstract] [PDF]


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