Proteins, interaction with platinum

Chaney SG, Campbell SL, Temple B, et al. Protein interactions with platinum-DNA adducts from structure to function. J Inorg Biochem 2004 98 1551-1559. 

In this section we summarise the manner in which i -metals. Fig. 6, and where possible specifically the platinum complexes of concern here, interact with biological molecules. Some radio-tracer studies have been carried out on the distribution of platinum complexes in whole bacteria grown in media inocculated with the metal ion. The results are summarised in Table 11. It is noteworthy that the bacteriocidal complex [PtClg]2- was taken up almost entirely by the cytoplasmic protein whereas the filamentous forming neutral species, [Pt(NHs)2Cl4], was... 

Glutathione readily replaces the GSMe on platinum in the reaction with [Pt(dien)(GSMe)]2+ (GSMe = S-methylglutathione) - this system is claimed to be an effective model for cisplatin-protein interaction 224). Rate constants and activation parameters have been... 

Nonsteroidal antiinflammatory drugs, interaction with lithium, 36 66 No-phonon transition, 35 324 Norbomadiene complexes with cobalt, 12 286 with copper, 12 328, 330, 331 with gold, 12 348, 349 with group VIB metals, 12 231 with group VnB metals, 12 241 with iron, 12 265 with palladium, 12 314 with platinum, 12 319 with rhodium, 12 300-302 with ruthenium, 12 278, 279 with silver, 12 340-342, 344, 346 Norbomylsiloxane, 42 226, 228 Notch receptor proteins, 46 473, 475 h (N)" oxime complexes, osmium, 37 260 h (N,0) oxime complexes, osmium, 37 260 (NPr ljiFeCfrdto),], magnetization versus temperature, 43 230... 

The high affinity of many platinum compounds for sulfur and the availability of many sulfur-containing biomolecules have raised the question whether Pt-sulfur biomolecule interactions could serve as a drug reservoir for platination at DNA, necessary for the antitumor activity of cis-Pt. Two reaction paths are possible, i.e., spontaneous release of plantinum from the sulfur, or nucleophilic displacement of platinum from sulfur by guanine (N7), for example. At the moment, there is no real evidence for the existence of such reactivation mechanisms. In fact, it has been reported that Pt-protein interactions in the plasma (albumin) are not reversible under normal conditions (161, 165). Further, a mixture of cis-Pt-methionine products does not show antitumor properties (166), indicating no induced platination of DNA. More research is required to investigate the existence of a reactivation mechanism. However, it is predicted that if such a reactivation phenomenon is operational, the most likely candidate is the labile Pt-methionine bond, as has been shown by its rapid reaction with Naddtc, STS, and thiourea (vide supra) (131). 

Some elements found in hody tissues have no apparent physiological role, hut have not been shown in he toxic. Examples arc rubidium, strontium, titanium, niobium, germanium, and lanthanum. Other elements are toxic when found in greater than trace amounts, and sometimes in trace amounts. These taller elements include arsenic, mercury, lead, cadmium, silver, zirconium, beryllium, and thallium. Numerous irlhcr elements are used in medicine in non-nulrieni roles. These include lithium, bismuth, antimony, bromine, platinum, and gold. The interactions of mineral nutrients with carbohydrates, fats, and proteins, minerals with vitamins (qv). and mineral nutrients with toxic elements are areas of active investigation. 

Inhibition of DNA synthesis. The significance of the interaction of platinum compounds with cellular DNA is apparent from studies of drug effects on macromolecular synthesis. Cis-DDP selectively and persistently inhibits the rate of DNA synthesis as compared with effects on RNA and protein synthesis in cells in culture (60-63) and cells in vivo (64,65). 

INTERACTION OF PLATINUM AGENTS WITH AMINO ACIDS, PEPTIDES AND PROTEINS... 

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