Liporetro-D-peptides - a novel class of highly selective thrombin inhibitors.

Introduction: Plasma serine protease thrombin plays a key role in coagulation, haemostasis and thromboembolic diseases. Direct thrombin inhibitors could be beneficial for future anticoagulant therapy. We have synthesized and studied liporetro-D-peptides - efficient thrombin inhibitors resistant to enzymatic degradation.

Influence of aromatic and aliphatic moieties on thrombin inhibitors potency.

Thrombin is a plasma serine protease that plays a key role in coagulation and hemostasis but also in thromboembolic diseases. Direct thrombin inhibitors could be beneficial for future anticoagulant therapy in the prophylaxis of venous and arterial thrombosis as well as myocardial infarction. To design the efficient thrombin inhibitors we have synthesized and studied peptide-based inhibitors resistant to enzymatic degradation.

Electrostatic effects in trypsin reactions. Influence of salts.

The influence of inorganic salts on trypsin-catalyzed reactions has been studied. It is shown that: (a) monovalent cations are reversible competitive inhibitors of tryptic hydrolysis of cationic substrates, whereas their binding has no effect on the reaction of neutral substrates; (b) a nonelectrostatic salt effect on the binding of both cationic and non-ionic substrates is caused by changes in the thermodynamic activity coefficient of the substrate; (c) the rate of trypsin active-site acylation is not affected by inorganic salts with monovalent cations. The data suggest that low-molecular-mass substrates are extracted into the enzyme microphase during substrate binding and further chemical transformations proceed without an access from surrounding medium.