Tag Archives: peptides
Chemical structure and properties of low-molecular furin inhibitors
T. V. Osadchuk1, O. V. Shybyryn1, V. K. Kibirev1,2
1Institute of Bioorganic Chemistry and Petrochemistry,
National Academy of Sciences of Ukraine, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: osadchuk@bpci.kiev.ua
The review is devoted to the analysis of the relationship between a chemical structure and properties of low-molecular weight inhibitors of furin, the most studied proprotein convertase, which is involved in the development of some pathologies, such as oncologic diseases, viral and bacterial infections, etc. The latest data concerning the influence of peptides, pseudo-peptides, aromatic and heterocyclic compounds, some natural ones such as flavonoids, coumarins, and others on enzyme inactivation are considered. The power of furin inhibition is shown to rise with the increasing number of positively charged groups in the structure of these compounds. Peptidomimetics (Ki = 5-8 pM) are shown to be the most effective furin inhibitors. The synthesized substances, however, have not been used in practical application yet. Nowadays it is very important to find more selective inhibitors, improve their stability, bioavailability and safety for the human organism.
Inhibition of fibrin polymerization by synthetic peptides corresponding to Аα195-205 and γ69-77 sites of fibrin molecule
T. A. Pozniak, L. P. Urvant, P. G. Gritsenko, V. I. Chernishov,
N. A. Pydiura, E. V. Lugovskoi, S. V. Komisarenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: lougovskoy@yahoo.com
Using the idea of “proline brackets” we have found four sites in fibrin amino acid sequence, and appropriate peptides were synthesized: γ69NPDESSKPN77, Bβ228QPDSSVKPY236, Bβ455RPFFPQ460 and Aα195LPSRDRQHLPL205. Turbidity and electron-microscopy analyses have demonstrated that synthetic peptide Аα195-205 specifically inhibited the stage of fibrin protofibril formation and peptide γ69-77 – the stage of fibrin protofibril lateral association. The data obtained testify that there are the sites involved in these processes in the appropriate amino acid sequences of fibrin molecule.