Hybrid analogues of SFTI-1 modified in P sub(1) position by beta - and gamma -amino acids and N-substituted beta -alanines

• Published in: Biopolymers Vol. 100; no. 2; pp. 154 - 159
• Main Authors: Debowski, D, ukajtis, R, Filipowicz, M, Strzelecka, P, Wysocka, M, gowska, A, Lesner, A, Rolka, K
• Format: Journal Article
• Language: English
• Published: 01.04.2013
• Subjects: Helianthus
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/bip.22184

A series of compounds containing either non-proteinogenic beta -/ gamma -amino acids or N-substituted beta -alanine residues ( beta -peptoid units) in P sub(1) specificity position were synthesized based on the structure of sunflower trypsin inhibitor 1 (SFTI-1). The compounds were synthesized on a solid support; the N-substituted beta -alanines ( beta Nhlys and beta Nhphe) were introduced into a peptidomimetic chain via a two-step approach using acryloyl chloride and an appropriate primary amine. The inhibitory activities were characterized in vitro against bovine alpha -chymotrypsin or bovine beta -trypsin. Three analogues displayed activity comparable to fully proteinogenic counterparts-monocyclic SFTI-1 and [Phe super(5)]SFTI-1. Moreover, all active peptidomimetics were resistant toward proteolytic degradation, even after 24-h incubation at room temperature. [copy 2012 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 154-159, 2013.