Analogues of Ecballium elaterium Trypsin Inhibitor II (EETI-II) with L-Cysteine Residues Substituted by L-Penicillamine (Pen) and L-Homocysteine (Hcy) in Positions 19, 21 and 27

• Autorzy: Frąszczak P. , Kaźmierczak K. , Stawikowski M. , Jaśkiewicz A. , Kupryszewski G. , Rolka K.
• Języki publikacji: EN

Abstrakty

EN

Two analogues of peptidic trypsin inhibitor isolated from seeds of Ecballium elaterium (EETI-II): [Pen19,21,27] EETI-II (1) and [Hcy19,21,27] EETI-II (2) were synthesized by the solid-phase method using the Fmoc/But procedure. Their inhibitory activity was determined by the calculation of association equilibrium constants (Ka) with bovine _-trypsin. In comparison with the parent compound, both analogues showed reduced trypsin inhibitory activity more than 7 and 18 times, respectively. We postulate that the observed differences may reflect the role of disulfide bridges in the interaction of inhibitors with trypsin or the introduced modifications change the conformational equilibrium of the analogues synthesized towards conformation(s) less favorable for the interaction with the enzyme.

Słowa kluczowe

EN

peptide tripsin inhibitors; solid phase peptide synthesis; analogues of EETI-II

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Polish Journal of Chemistry
• Rocznik: 2002
• Tom: Vol. 76 / nr 10
• Strony: 1441--1446
• Opis fizyczny: Bibliogr. 15 poz., rys.

Twórcy

autor

Frąszczak P.

• Faculty of Chemistry, University of Gdańsk, 80-952 Gdańsk, Sobieskiego 18, Poland

autor

Kaźmierczak K.

• Faculty of Chemistry, University of Gdańsk, 80-952 Gdańsk, Sobieskiego 18, Poland

autor

Stawikowski M.

• Faculty of Chemistry, University of Gdańsk, 80-952 Gdańsk, Sobieskiego 18, Poland

autor

Jaśkiewicz A.

• Faculty of Chemistry, University of Gdańsk, 80-952 Gdańsk, Sobieskiego 18, Poland

autor

Kupryszewski G.

• Faculty of Chemistry, University of Gdańsk, 80-952 Gdańsk, Sobieskiego 18, Poland

autor

Rolka K.

• Faculty of Chemistry, University of Gdańsk, 80-952 Gdańsk, Sobieskiego 18, Poland

Bibliografia

• 1. Wilusz T., Wieczorek M., Polanowski A., Denton A„ Cook J. and Laskowski M. Jr. Hoppe-Sevler i Z Physiol. Chem., 356, 93 (1983).
• 2. Wieczorek M„ Otlewski J„ Cook J, Parks K„ Leluk J„ Wiiimowska-Pelc A., Polanowski A., Wilusz T. and Laskowski M, Jr., Biochem. Biophys. Res. Commun., 126, 646 (1985).
• 3. Otlewski J., Krowarsch D. and Apostoluk W., Acta Biochim. Pol., 46, 531 (1999).
• 4. Kupryszewski G., Ragnarsson U., Rolka K., Wilusz T. and Polanowski A, Int. J. Pept. Protein Res., 27, 245 (1986).
• 5. Kupryszewski G., Rolka K., Różycki J. and Ragnarsson U., Polish J. Chem., 68,879(1994)and publications cited therein.
• 6. Kupryszewski G. and Rolka K., Cucurbita maxima trypsin inhibitor I and III (CMTI-I and III). Structure-activity relationship studies, in Hellenie Forum on Bioactive Peptides (P.A Cordopatis ed.) Crete University Press, Heraklion 1997, p. 193 and publications cited therein.
• 7. Szyk A., Lesner A., Rolka K. and Kupryszewski G., Polish J. Chem., 70, 1522 (1996)
• 8. Favel A., Mattras H., Coletti-Priviero M.A., Zwilling R., Robinson E.A. and Castro B., Int. J. Pept. Protein Res., 33,202 (1989). '
• 9. Favel A., Le-Nguygen D., Coletti-Priyiero M.A. and Castro B., Biochem. Biophys. Res. Commun., 162.
• 10. Bode W., Greyling H.J., Huber R., Otlewski J. and Wilusz T., FEBSLett., 242, 285 (1989).
• 11. Holak T.A., Gondol D., Otlewski J. and Wilusz T., J. Mol. Biol., 210, 635 (1989).
• 12. Jaśkiewicz A. , Lesner A., Różycki J., Kupryszewski G. and Rolka K„ Polish J. Chem., 72,2537(1998).
• 13. Zhang W.J.,Nikiforovich G., Perodin J„ Richard D.E., EscherE, and Marshall G.R., J. Med. Chem., 39, 2738 (1996J,
• 14. Frąszczak P., Rolka K. and Kuptyszewski G., Polish J. Chem., 76, 519 (2002).
• 15. Rajarathnam K., Sykes B.D., Dewald B.,Baggiolini M. and Clark-Lewis l., Biochem., 38, 7653 (1999).