Tag Archives: substrates

Role of charge and hydrophobic effects in reactions of peptide substrates and inhibitors with thrombin

A. A. Poyarkov, V. V. Prokopenko, S. A. Poyarkova

Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: alexp@bpci.kiev.ua

A substrate and inhibitor analysis of the thrombin interaction with synthetic peptide substrates and inhibitors of differing hydrophobicity and volume of the side amino acid residue, locali­zed in the sub-centers thrombin S2 and S3 were carried out. The kinetic parameters of individual stages of the enzymatic reaction process (Ks, k2, k3) were estimated. It is shown that the efficiency of acylation and deacylation stages of the enzymatic reaction decreases with increasing hydrophobicity of the substituent in P2 as well as P3, at the same time the affinity of selected peptides toward enzyme is steadily increasing.
With the aim to evaluate the hydrophobicity of compounds a LogP value was calculated and was made an attempt to compare them with the correspondent Ki values. Comparative kinetic analysis of Z-Arg-OMe and its uncharged analogue Z-Cit-OMe has shown the absence of uncharged analog hydrolysis, however, the mentioned citrulline derivate inhibits the hydrolysis of the charged analogue. These findings confirm the important role of hydrophobic moiety in the structure of thrombin inhibitors in preferential binding mode and inhibition of thrombin active side.

Inhibitory effect of benzimidazole derivatives on cholinesterases of animals in the presence of different substrates

N. E. Basova, B. N. Kormilitsyn, A. Yu. Perchenok,
E. V. Rozengart, V. S. Saakov, A. A. Suvorov

Sechenov Institute of Evolutionary Physiology and Biochemistry,
Russian Academy of Science, Saint-Petersburg;
e-mail: roz@iephb.ru

Specifically synthesized group of benzimid­azole derivatives possessing varying degrees of delocalization of the positive charge in the cation group of the molecule has been studied in order to search for potential cholinergically active compounds and to study the role of the Coulomb interaction in cholinesterase catalysis. These compounds were reversible inhibitors of cholinesterase (ChE) of human erythrocytes, horse serum, brain of the frog Rana temporaria­ and visual ganglia of the Pacific squid Todarodes pacificus in the presence of acetylthio­choline iodide and propionylthiocholine iodide as substrates. The differences in the nature of reversib­le inhibitory effect were observed. The effect of the inhibitor structure and substrate nature, specific for each of the studied inhibitors, on the character of the process of reversible inhibition was found.