Fourteen monocyclic analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds were synthesized by the solid-phase method. The purpose of this work was to establish the role of a disulfide bridge present in inhibitor's side chains of Cys3 and Cys11 in association with serine proteinases. This cyclic fragment was replaced by the disulfide bridges formed by L-pencillamine (Pen), homo-L-cysteine (Hcy), N-sulfanylethylglycine (Nhcy) or combination of the three with Cys. As in the substrate specificity the P(1) position of the synthesized analogues Lys, Nlys [N-(4-aminobutyl) glycine], Phe or Nphe (N-benzylglycine) were present, and they were checked for trypsin and chymotrypsin inhibitory activity. The results clearly indicated that Pen and Nhcy were not acceptable at the position 3, yielding inactive analogues, whereas another residue (Cys11) could be substituted without any significant impact on the affinity towards proteinase. On the other hand, elongation of the Cys3 side chain by introduction of Hcy did not affect inhibitory activity, and an analogue with the Hcy-Hcy disulfide bridge was more than twice as effective as the reference compound ([Phe(5)] SFTI-1) in inhibition of bovine alpha-chymotrypsin. (C) 2010 Elsevier Ltd. All rights reserved.
Authors
- Anna Łęgowska,
- Dawid Dębowski,
- Łukajtis Rafał,
- Magdalena Wysocka,
- Dr hab. Cezary Czaplewski,
- Adam Lesner link open in new tab ,
- Krzysztof Rolka,
- Rafał Łukajtis link open in new tab
Additional information
- DOI
- Digital Object Identifier link open in new tab 10.1016/j.bmc.2010.10.014
- Category
- Publikacja w czasopiśmie
- Type
- artykuł w czasopiśmie wyróżnionym w JCR
- Language
- angielski
- Publication year
- 2010
