Abstract.
The DNA binding profiles of three bis Pt(II) polyamine-linked compounds, [{trans-PtCl(NH3)2}2{µ-spermine-N 1,N 12}]4+, [{trans-PtCl(NH3)2}2{µ-spermidine-N 1,N 8}]3+, and [{trans-PtCl(NH3)2}2{µ-BOC-spermidine}]2+, were compared with that of a novel trinuclear phase II clinical agent, [{trans-PtCl(NH3)2}2{µ-trans-Pt(NH3)2(H2N(CH2)6NH2)2}]4+. All of the compounds bind preferentially in a bifunctional manner, according to unwinding of supercoiled DNA circles. The kinetics of binding of these compounds corresponds to their relative charge (2+ to 4+). The preference for the formation of interstrand crosslinks, however, does not follow a charge-based pattern. By studying the results of DNA polymerase extension products on a DNA template modified by the compounds, and by incorporating the complementary method of RNA transcription mapping, it was possible to determine the nucleotide bases that are preferred sites of binding. The stop sites due to platinum adducts were determined, and some preliminary observations concerning the range and type of crosslinks were established. It can be concluded that dinuclear Pt compounds are similar to their trinuclear counterpart, and that charge differences do not contribute solely to the variances between the compounds.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Electronic Publication
Rights and permissions
About this article
Cite this article
McGregor, T.D., Hegmans, A., Kašpárková, J. et al. A comparison of DNA binding profiles of dinuclear platinum compounds with polyamine linkers and the trinuclear platinum phase II clinical agent BBR3464. J Biol Inorg Chem 7, 397–404 (2002). https://doi.org/10.1007/s00775-001-0312-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00775-001-0312-4