| Abstract
| - The determination of the structures and DNA interactions and the reactions with GSH and ubiquitin ofcomplexes of the general formula trans-[PtCl2(Am)(pip-pip)]·HCl, where pip-pip is 4-piperidinopiperidineand Am is NH3, methylamine (MA), dimethylamine (DMA), n-propylamine (NPA), isopropylamine (IPA),n-butylamine (NBA), or cyclohexylamine (CHA), were performed. X-ray structures and NMR studies ofthe NH3 and MA complexes showed that both pip rings were in the chair conformation and that the secondpip ring is fluxional. The DNA binding studies showed that these complexes bind to calf thymus DNAnearly an order of magnitutde more quickly than cisplatin and form covalent adducts that stabilize the doublehelix. The binding of the pip-pip complexes to DNA results in high unwinding angles (∼30°) and in theformation of ∼25% interstrand cross-links. The pip-pip complexes reacted with GSH more quickly thancisplatin and transplatin, and the rate of reaction decreased with increasing steric bulk of the ligand trans tothe pip-pip. The reactions with ubiquitin resulted in monofunctional binding to Met1. Only the NH3, MA,and DMA complexes reacted with ubiquitin in a slower and less efficient fashion than cisplatin.
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