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Ferrocenylalkyl nucleobases (1-14) were prepared via the reaction of the α-(hydroxy)alkyl ferrocenes FcCHR(OH) (Fc = ferrocenyl; R = H, Me, Et, Ph) with thymine, cytosine, iodo-cytosine and adenine in DMSO at 100• C, yields being 50-80%. The antitumor activities of ferrocenylmethyl thymine (1) against solid tumor models, carcinoma 755 (Ca755) and Lewis lung carcinoma (LLC) were studied in vivo. Therapeutic synergism of antitumor activity against LLC was demonstrated in the case of combined application of compound 1 with anticancer drug cyclophosphamide.

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Pyridoxal 5'-phosphate-dependent methionine gamma-lyase (MGL) is involved in the metabolism of sulfur-containing amino acids. The enzyme is a promising target in some anaerobic pathogens and is effective in cancer-cell treatment. The structure of the MGL holoenzyme from Citrobacter freundii has previously been determined at 1.9 A resolution. By modification of the crystallization procedure, the previously determined structure of C. freundii MGL has been improved to 1.35 A resolution with R and R(free) values of 0.152 and 0.177, respectively. This high-resolution structure makes it possible to analyze the interactions between the monomers in detail and to reveal the structurally invariant regions that are responsible for monomer-monomer recognition during the formation of the active enzyme. Details of the mode of cofactor binding and of the flexible regions that may be involved in substrate recognition and binding are also described.

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Kinetic parameters of Citrobacter freundii methionine γ-lyase were determined with substrates in γ-elimination reactions as well as the inhibition of the enzyme in the γ-elimination of L-methionine by amino acids with different structure. The data indicate an important contribution of the sulfur atom and methylene groups to the efficiency of binding of substrates and inhibitors. The rate constants of the enzyme-catalyzed exchange of C-α- and C-β-protons with deuterium were determined, as well as the kinetic isotope effect of the deuterium label in the C-α-position of inhibitors on the rate of exchange of their β-protons. Neither stereoselectivity in the β-proton exchange nor noticeable α-isotope effect on the exchange rates of β-protons was found. The ionic and tautomeric composition of the external Schiff base of methionine γ-lyase was determined. Spectral characteristics (absorption and circular dichroism spectra) of complexes with substrates and inhibitors were determined. The spectral and kinetic data indicate that deamination of aminocrotonate should be the rate-determining stage of the enzymatic reaction.

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