AVS 52nd International Symposium
    DNA Topical Conference Monday Sessions
       Session DN-MoP

Paper DN-MoP8
Hybridization of Platinum Drug Adducts

Monday, October 31, 2005, 5:00 pm, Room Exhibit Hall C&D

Session: DNA Poster Session
Presenter: L. Postelnicu, Boston University
Authors: L. Postelnicu, Boston University
R.M. Georgiadis, Boston University
Correspondent: Click to Email
Hybridization of platinum drug adducts DNA is generally considered the major pharmacological target of platinum drugs. As such it is of considerable interest to understand the patterns of DNA perturbation. The new antitumor trinuclear platinum compound [{trans-PtCl(NH3)2}2µ-trans-Pt(NH3)2{H2N(CH2)6NH2}2]4+ (designated as BBR3464) is a highly charged compound, non-cross resistant with cisplatin in many human tumor xenografts. The enhanced binding of BBR3464 to single stranded DNA and RNA substrates suggests additional pathways for disrupting cellular function different from the traditional cisplatin. Single strand DNA is present during replication, transcription, recombination and repair. Here, we investigate how DNA hybridization is perturbed by the presence of a single platinum drug bound to one of the DNA strands, using BBR3464 and cisplatin DNA adducts. We use surface plasmon resonance (SPR) spectroscopy to monitor both free DNA and DNA adducts hybridization to a surface immobilized complementary DNA strand. We characterize and compare the hybridization rate constants of cisplatin and BBR3464 DNA adducts at different ionic strength. BBR3464 is a large and highly charge structure compared to cisplatin. The results suggest that the charge of the drug is less important in the hybridization event, and the steric hindrances due to different structures may be more important for hybridization efficiency and kinetics.