[Inhibition of penicillin acylase from Escherichia coli by benzylalkylketones and benzylalkylcarbinols]. / Ingibirovanie benzilalkilketonami i benzilalkilkarbinolami penitsillinatsilazy iz Escherichia coli.

A number of benzylalkylketones and benzylalkylcarbinols have been synthesized as non-hydrolizable substrate analogues of penicillin acylase (EC 3.5.1.11), and their affinity to the enzyme has been studied. The compounds with plane trigonal carbonyl group (ketones) were established to has bind to the enzyme 20-40 times more tightly than their tetrahedral counterparts with a hydroxyl function (carbinols). 4-Oxo-5-phenylpentanoic acid was found to be one of the most potent reversible competitive inhibitors of penicillin acylase with Ki-31 microM.

[Phosphorus-containing inhibitors of penicillin acylase. 4. Irreversible inhibition of penicillin acylase from Escherichia coli by monoaryl esters of benzylphosphonic acid]. / Fosfor-soderzhashchie ingibitory penitsillinatsilazy. 4. Neobratimoe ingibirovanie penitsillinatsilazy iz Escherichia coli monoarilovymi éfirami benzilfosfonovoi kisloty.

Monoaryl of benzylphosphonic acid have been synthesized and studied as the inhibitors of penicillin acylase. These compounds were found to be effective and selective irreversible inhibitors of the enzyme. The kinetic parameters of enzyme inactivation are determined, and possible mechanism of the inhibition is discussed. These phosphonates should be useful as both penicillin acylase active site titrants and the tools for the enzyme function study. Benzylchloromethyl keton has been also prepared and it is an irreversible inhibitor of penicillin acylase.

[Phosphorus-containing inhibitors of penicillin acylase. 3. Inhibition of Escherichia coli penicillin acylase by phosphonate analogs of substrates]. / Fosforsoderzhashchie ingibitory penitsillinatsilazy. 3. Ingibirovanie penitsillinatsilazy Escherichia coli fosfonatnymi analogami substratov.

Phosphonic analogues of penicillin acylase substrates are found to be selective reversible competitive inhibitors of the enzyme from E. coli (EC 3.5.1.11). The mode of binding of the inhibitors to the enzyme and the influence of the stereoelectronic parameters of the phosphonic inhibitors on their affinity to the enzyme are discussed.

[Phosphorus-containing inhibitors of penicillin acylase. 2. Design, synthesis and study of the hydrolytic stability of phosphonic acid derivatives as potential inhibitors of penicillin acylase]. / Fosforsoderzhashchie ingibitory penitsillinatsilazy. 2. Dizain, sintez i izuchenie gidroliticheskoi stabil'nosti proizvodnykh fosfonovykh kislot kak potentsial'nykh ingibitorov penitsillinatsilazy.

Phosphonate and phosphonoamidate derivatives of benzylphosphonic acids were synthesized as potential inhibitors of penicillin acylase (EC 3.5.1.11) proceeding from the concept of transition-state analogues. The compounds obtained are not the substrates of the enzyme and they are stable under conditions of enzyme activity testing.

[Kinetic characteristics and enantioselective action of penicillinase in the hydrolysis reaction of N-phenylacetyl derivatives of 1-aminoethylphosphonic acid and its esters]. / Kineticheskie zakonomernosti i énantioselektivnost' deistviia penitsillinazy v reaktsii gidroliza N-fenilatsetil'nykh proizvodnykh 1-aminoétilfosfonovoi kisloty i ee éfirov.

Penicillin acylase from E. coli (EC 3.5.1.11) was found to hydrolyze N-phenylacetylated 1-aminoethylphosphonic acid and its esters. The enzyme preferentially converts the R-form of the substrates: the ratios of the bimolecular rate constants of penicillin acylasecatalyzed hydrolysis of R- and S-forms of 1-(N-phenylacetamino)-ethylphosphonic acid and its dimethyl- and diisopropyl-esters are 58000, 2300, 1800; these derivatives were shown to have the greatest values of the catalytic constants for enzymatic hydrolysis of all known substrates for penicillin acylase: 237, 148 and 134 s-1; the corresponding Km values are 3.7 10(-5), 6.8 10(-4) and 6.2 10(-4) M at pH 7.0. The kinetics of enzymatic hydrolysis of 1-(N-phenylacetamino)-ethylphosphonic acid was investigated up to high degrees of conversion. The inhibition of penicillin acylase by high concentrations of the R-form of the substrate (with substrate inhibition constant of 0.07 M) and competitive inhibition by the reaction product, phenylacetic acid (Ki = 3.5 10(-5) M), was observed.

[Activation of 5-lipoxygenase by lipophilic n-alkyl-containing acids--an allosteric process]. / Aktivatsiia 5-lipoksigenazy lipofil'nymi n-alkilsoderzhashchimi kislotami--allostericheskii protsess.

Mechanism of the activation of 5-lipoxygenase (EC 1.13.11.12) has been investigated and shown to have the allosteric character. Limitations of the activator structure are formulated.

[biological activity of phosphorus analogs of amino acids]. / Biologicheskaia aktivnost' fosfornykh analogov aminokislot.

Data available in literature on biological activity of the phosphorus analogues of amino acids are summarized. The most typical kinds of bioactivity of aminophosphonic, aminophosphinic and aminophosphonous acids are characterized. These compounds, both natural and synthetic, are shown to possess a wide spectrum of bioactivity and may be estimated as potential bioregulators.