Analogues of trypsin inhibitor SFTI-1 modified in the conserved P1′ position by synthetic or non-proteinogenic amino acids retain their inhibitory activity
✍ Scribed by Łukajtis Rafał; Łȩgowska Anna; Wysocka Magdalena; Dȩbowski Dawid; Lesner Adam; Rolka Krzysztof
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 177 KB
- Volume
- 17
- Category
- Article
- ISSN
- 1075-2617
- DOI
- 10.1002/psc.1330
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✦ Synopsis
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 α‐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 © 2011 European Peptide Society and John Wiley & Sons, Ltd.