1. Analogues of trypsin inhibitor SFTI-1 modified in the conserved P1 ′ position by synthetic or non-proteinogenic amino acids retain their inhibitory activity
- Author
-
Dȩbowski Dawid, Łukajtis Rafał, Wysocka Magdalena, Łȩgowska Anna, Lesner Adam, and Rolka Krzysztof
- Subjects
Pharmacology ,chemistry.chemical_classification ,Chemistry ,Stereochemistry ,Trypsin inhibitor ,Non-proteinogenic amino acids ,Organic Chemistry ,Disulfide bond ,Peptide ,General Medicine ,Inhibitory postsynaptic potential ,Biochemistry ,Chemical synthesis ,chemistry.chemical_compound ,Structural Biology ,Drug Discovery ,Glycine ,Molecular Medicine ,Molecular Biology ,Derivative (chemistry) - Abstract
A series of linear and monocyclic (with a disulfide bridge only) analogues of trypsin inhibitor SFTI-1 modified in the P-1 and/or P-1' positions were synthesized by the solid-phase method. In the substrate specificity P-1 position, Phe or N-benzylglycine (Nphe) were introduced, whereas the conserved Ser6 in Bownam-Birk (BBI) inhibitors was replaced by Hse (L-homoserine), Nhse [N-(2-hydroxyethyl)glycine], Sar, and Ala. Kinetic studies of interaction of the analogues with bovine alpha-chymotrypsin have shown that in monocyclic (but not linear) analogues, Hse and Nhse are tolerated to afford potent inhibitors. This is the first evidence that the absolutely conserved Ser present in the inhibitor's P-1' position can be successfully replaced by a synthetic derivative. Copyright (C) 2011 European Peptide Society and John Wiley & Sons, Ltd.
- Published
- 2011