[Purification of acetylcholinesterase from human erythrocytes using metal-chelate affinity chromatography]. / Ochistka atsetilkholinésterazy iz éritrotsitov cheloveka s pomoshch'iu metallo-khelat affinnoi khromatografii.

Acetylcholinesterase (AChE) was purified on columns with iminodiacetate Agarose charged with Cu2+, Zn2+, and Ni2+. The best results (a 14-fold purification and more than 30% activity yield) were obtained with Zn2+ used as a complex-forming metal. The preparation had a specific activity of approximately 7 U. Its purity was tested by polyacrylamide gel electrophoresis under denaturing conditions.

[Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid]. / Ingibirovanie aktivnosti kholinésteraz ftorsoderzhashchimi proizvodnymi alpha-aminofosphonovykh kislot.

A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.

[Formation of models of the interaction between organophosphate compound structure and their ability to inhibit cholinesterase]. / Formirovanie modelei vzaimosviazi mezhdu strukturoi fosfororganicheskikh soedinenii i ikh sposobnost'iu k ingibirovaniiu kholinésteraz.

On the basis of a discrete-regression model earlier proposed by the authors, computer modelling of relationships between structure of organophosphorous compounds and their anticholinesterase activity was carried out. Values of kinetic constants of reversible and irreversible inhibition of human erythrocyte acetylcholinesterase and horse serum butyrylcholinesterase by more than 240 phosphoryl and thiophosphoryl compounds (from own and literature data) were used as initial basis. For description of these compounds' structure informational-topological, physico-chemical and donor-acceptor descriptors were used. By means of procedures of discriminant, regression and cluster analysis, the compounds studied were divided into groups according to the structure, and quantitative structure--activity correlations were found in most of the clusters. This study revealed some functional peculiarities of these compounds and allowed for rationalisation of search of effective compounds with anticholinesterase activity.