The effect of ε-aminocaproyl-S-benzyl-L-cysteine on the t-PA activity of human saliva.

PURPOSE: The aim of this work was to study the effect of the synthetic antifibrinolytics: ε-aminocaproic acid (EACA), tranexamic acid (AMCHA) and ε-aminocaproyl-S-benzyl-L-cysteine (H-EACA-S-Bzl-L-Cys-OH) on the fibrinolytic activity of saliva in order to obtain new data on the activity of saliva tissue plasminogen activator (t-PA). MATERIAL AND METHODS: Saliva samples were obtained from healthy volunteers. Saliva, precipitate and supernatant were tested 1hr, 4 hrs and 6hrs after collection. The effect of the synthetic antifibrinolytics was examined with the use of the clot lysis time determination. RESULTS: All examined compounds inhibited the fibrinolytic activity of saliva 1hr after collection. H-EACA-S-Bzl-L-Cys-OH was the most active inhibitor. After 6 hours in room temperature only this compound showed a certain possibility to prolong the clot lysis time. CONCLUSIONS: The obtained results may indicate the possibility of the difference in specificity between the activities of t-PA of saliva and recombinant tissue plasminogen activator activities. It may explain the unexpected high inhibitory activity of H-EACA-S-Bzl-L-Cys-OH in our study.

Effects of S-hexyl-L-cysteine derivatives on prothrombin activation and clotting time determined in the presence of heparin.

PURPOSE: The aim of the study is the examination of effects of dipeptides containing S-hexyl-L-cysteine and glycine, on the prothrombin activation and the thrombin clotting time determined in the presence of heparin. MATERIAL AND METHODS: The activation of prothrombin was determined with the use of the thromboplastin test, the recalcification and partial thromboplastin with kaolin tests. The thrombin clotting time determined in the presence of heparin was evaluated with the use of the heparin-thrombin test. RESULTS: The investigated derivatives slightly inhibited the prothrombin activation. The unsubstituted derivatives and dipeptides with a free amino or carboxyl group significantly enhanced the clotting time determined in the presence of heparin at concentration 20 mM. S-Hexyl-L-cysteinylglycine (H-(S-hexyl)-L-Cys-Gly-OH) was the most active compound. CONCLUSIONS: The obtained results indicate that some dipeptide derivatives of S-hexyl-L-cysteine apart from the earlier observed possibility to prolong the thrombin clotting time, can also prolong the clotting time determined in the presence of heparin.

Short peptides containing L-lysine and epsilon-aminocaproic acid as potential plasmin inhibitors.

Eight short peptides containing L-lysine and epsilon-aminocaproic acid were obtained and their effect on the amidolytic activities of plasmin, thrombin and trypsin was examined. Tripeptide amide Boc-EACA-L-Lys-EACA-NH2 was the most effective and specific plasmin inhibitor.

Methylketone inhibitors of plasmin.

A series of peptide methylketones with generalformula Y-Phe-Lys-CH3 was prepared as potential inhibitors of plasmin.

Synthesis of benzylamides of dipeptides as potential inhibitors of plasmin.

Four benzylamides of dipeptides with the general formula: X-L-Lys-NH-CH2-C6H5, where X = L-or D-Leu and L-or D-Phe were prepared as potential inhibitors of plasmin. All of them influenced on the fibrynolytic activity of plasmin, but only D-Leu-L-Lys-NH-CH2-C6H5 inhibited the amidolytic activity of this enzyme. None of the tested compounds was an inhibitor of thrombin in an amidolytic test.

Effect of epsilon-aminocaproylaminoacids on the activity of proteolytic enzymes.

Effect of three epsilon-aminocaproylaminoacids with significant antifibrinolytic activity on chymotrypsin, trypsin, cathepsin B, cathepsin C and cathepsin D activities was examined. Slight inhibition of trypsin and chymotrypsin activity was observed only at high concentrations of these compounds. All tested dipeptides did not influence activities of cathepsin B, cathepsin C and cathepsin D.

Interaction of L-gamma-glutamyl-alpha,beta-dehydroamino acids with gamma-glutamyl transpeptidase.

Three gamma-glutamyl alpha,beta-dehydroamino acids: L-gamma-glutamyl-dehydroalanine, L-gamma-glutamyl-(Z)-dehydrobutyrine and L-gamma-glutamyl-(E)-dehydrobutyrine have been prepared as potential ligands (inhibitors or substrates) for gamma-glutamyl transpeptidase (GGT). Both isomers of gamma-glutamyl-dehydrobutyrines proved to be inhibitors of GGT, slightly better than the saturated analogue, L-gamma-glutamyl-L-butyrine. However, their solvolysis catalysed by the enzyme is slower than that of the latter. L-gamma-Glutamyl-(E)-dehydrobutyrine seems to be a more active compound in both enzymatic tests. L-gamma-Glutamyl-dehydroalanine elicited only low inhibitory activity and, moreover, was unstable under conditions of the solvolysis test.

The influence of epsilon-aminocaproic acid derivatives on the anticoagulant activity of heparin.

Derivatives of epsilon-aminocaproic acid with antifibrinolytic activity, at low concentration, do not influence the anticoagulant activity of heparin under the heparin-thrombin test conditions. At concentrations higher than 0.002 M tested compounds slightly enhance the anticoagulant action of heparin.

Effects of epsilon-aminocaproylaminoacids on prothrombin activation and thrombin activity.

Influence of four epsilon-aminocaproylaminoacids on prothrombin activation and thrombin activity was examined. Only epsilon-aminocaproylnorleucine markedly inhibited the prothrombin activation in an extrinsic system.

Tripeptide methylketones: synthesis and antiplasmin activity.

A series of tripeptide methylketones with C-terminal lysine was obtained via Dakin-West method and tested for their antiplasmin activity with the use of antifibrinolytic and antiamidolytic tests. The tripeptide methylketones has been found to inhibit plasmin, however with much lower potency than respective aldehydes.

Synthesis and activity of N epsilon-aminocaproyl-L-norleucine derivatives.

Five new derivatives of epsilon-aminocaproyl-L-norleucine were synthesized. Antifibrinolytic and anticaseinolytic activities were tested. All tested compounds were inhibitors of plasmin.

Influence of dipeptide derivatives of S-substituted cysteines on the time of fibrinolysis.

Amino acids containing sulphur, dipeptide derivatives of methionine and S-substituted derivatives of cysteine are potent antifibrinolytic agents. The structural moiety of the substances responsible for the effect on the clot formation is not known. Present study was undertaken in order to evaluate the effect of some analogues of dipeptides containing S-substituted derivatives of cysteine with the formula A-Cys(S-X)-Y (where A-amino acid, X-benzyl, butyl, hexyl, nonyl and Y-OH or OMe) on clot dissolution under the antifibrinolytic test conditions. It has been found that dipeptide derivatives of S-substituted cysteine (except benzyl derivative) at low concentration evoke antifibrynolytic activity, while at high concentration they prevent clot formation. The results suggest that antifibrinolytic activity of tested compounds at low concentration may be due to the formation of antifibrinolitycally active conformation, while high concentration overcome the effect.

Synthesis and activity of N alpha-(epsilon-aminocaproyl)-alanines and N epsilon-(epsilon-aminocaproyl)-caproic acid.

Four new dipeptides containing epsilon-aminocaproic acid were synthesized. Antibrinolytic, antiacaseinolytic activity and influence on activation of plasminogen by streptokinase were tested.

Synthesis and activity of dipeptides containing epsilon-aminocaproic acid.

Five new dipeptides containing epsilon-aminocaproic acid were synthesized. All dipeptides markedly inhibit fibrinolytic activity of plasmin but only in low concentration (0.0002M). In higher concentration fibrinolytic activity was observed. Activity of dipeptides containing epsilon-aminocaproic acid, which antifibrinolytic activity is known, was tested on plasmin, thrombin, urokinase and euglobulin fraction using synthetic substrates.

[Synthesis and properties of antifibrinolytic dipeptides containing E-aminocaproic acid]. / Synteza i wlasciwosci antyfibrynolityczne dipeptydów zawierajacych kwas E-aminokapronowy.

Three new dipeptides of E-aminocaproic acid were synthesized and their antifibrinolytic activity was examined. H-EACA-L-Trp-OH possess stronger antifibrinolytic activity than H-EACA-L-Tyr-OH and H-EACA-L-Leu-OH. Antifibrinolytic activity of H-EACA-L-Gly-OH was smallest.

Peptide inhibitors of plasmin.

Seven peptides of the general formula A-Phe-Lys-X or A-Phe-NH-(CH2)5-NH2 where A = Glp or Ala, X = -OH, -NHC7H15 or -OC7H15 were obtained. The peptide H-Ala-Phe-Lys-NHC7H15 markedly inhibits the fibrinolytic activity of plasmin. The antifibrinolytic activity of the peptide Glp-Phe-Lys-OC7H15 is similar to EACA. The both peptides only slightly activate the caseinolytic activity of plasmin.

[Relationship between structure and activity in antifibrinolytic peptides containing E-aminocaproic acid]. / Zaleznosc miedzy struktura a aktywnoscia antyfibrynolityczna peptydów zawierajacych kwas e-aminokapronowy.

New peptides containing E-aminocaproic acid were synthetized. Some conclusions on structure-activity relationship were made.