The Department of Protein Chemistry

Vladimir K. Kibirev, DPh, Doctor of Scienses, Professor;

Address: Institute of Bioorganic Chemistry and Petrochemistry, The Ukrainian National Academy of Sciences); Murmanskaya street 1, Kiev 02660, Ukraine;
Telephone: +380 (044) 573 27 28; Fax: +380 (044) 573 25 52;
E-mail: kibirev@bpci.kiev.ua

Scientific trends of the department:

The main scientific trend of the department is the study on physicochemical basis of functioning the proteolytic enzymes, particularly such serine proteinases, as thrombin - the key enzyme of clotting system, and trypsin. These investigations included the chemical and enzymatic synthesis of peptides containing natural amino acids and their analogs, preparation and purification of blood clotting enzymes, and their substrate and inhibitor analysis. On the basis of synthetic arginine-containing peptides (the inhibitors of thrombin) novel materials for affinity chromatography of human [alpha]-thrombin has been elaborated, and an effective method for preparation and purification of the enzyme and its proteolytic forms has been developed. Besides natural peptides, the use has been made of peptides, containing non-natural and non-proteinogenic amino acids, for instance, fluoroamino acids, aminophosphonic acids, isomers of aminobenzoic acids and derivatives of arginine including some heterocyclic systems.

Perspective investigations and elaborations:

During recent years new intramolecularly quenched fluorescent substrates for thrombin has been designed and synthesized. The peptidomimetics containing some heterocyclic systems are developed. In consequence with the arginine-containing peptide the synthesis of compounds having immunomodulating and fungistatic activity has been undertaken. The methods for synthesis of biological active peptidomometics stable to degradation by enzymes are developed. On the basis of these peptides some perspective drugs can be developed.

Additional information about the Department:

The main trends for collaboration are:
· Chemical synthesis of biologically active peptides, design of new chromogenic or fluorogenic substrates, novel inhibitors and ligands for affinity chromatography of proteolytic enzymes - thrombin, factor Xa, protein C;
· Preparation, purification and testing the blood clotting enzymes at normal or pathological states, and their substrate and inhibitor analysis;
· Design and development of novel diagnostics for assaying the proteolytic enzymes of haemostasis, and determination of their natural inhibitors;
· Synthesis of new biological active peptides that are the potential inhibitors of HIV-proteases.

Several articles published by the dept specialists during last five years are further cited:

1. Rita Gothe, Lydia Seyfarth, Christian Schumann, Inge Agricola, S. Reissmann, Axel Lifferth, Christian Birr, Magarita Pavlovna Filatova, Alexander Kritsky, Vladimir Kibirev. - Combination of allyl protection and HYCRAMTM-linker technology for the synthesis of peptides with problematical amino acids and sequences. - J. Prakt. Chem., 1999, v. 24, No 4, p. 369-377.
2. Kibirev V.K., Kholodovich V.V., Gershkovich A.A. - Peptidomimetics as low molecular weight inhibitors of thrombin - Drug and Pharmaceuticals Current R & D Highlights (Peptidomimetics), 2000, v. 23, No 3, p. 4-16 (Review).
3. Alexander A. Gershkovich, Sergey V. Verevka, Vladimir K. Kibirev, Alexander P. Demchenko. Solid-state conjugation of proteins with hydrophobic compounds in non-denaturing conditions. I. Acylation of proteins by dansyl proline using a polymeric N-hydroxysuccinimide ester. - J. Biochem. Biophys. Methods, 2000, vol. 45, pp. 183-191.
4. Poyarkova S.A., Fedoryak O.D., Kibirev V.K., Kukhar V.P. - Synthesis and antithrombin activity of phosphoalanine-containing peptides. - Russian J. Bioorganic Chem., 2003, V. 29, No 3, P. 247-253 (in Russian).