title: Hybrid analogues of SFTI-1 modified in P₁ position by β- and γ-amino acids and N-substituted β-alanines.
abstract: A series of compounds containing either non-proteinogenic β-/γ-amino acids or N-substituted β-alanine residues (β-peptoid units) in P1 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 β-alanines (βNhlys and βNhphe) 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 α-chymotrypsin or bovine β-trypsin. Three analogues displayed activity comparable to fully proteinogenic counterparts-monocyclic SFTI-1 and [Phe(5)]SFTI-1. Moreover, all active peptidomimetics were resistant toward proteolytic degradation, even after 24-h incubation at room temperature.
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, University of Gdansk, Sobieskiego 18, 80-952, Gdansk, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Debowski
authors.forename: R
authors.initials: R
authors.lastname: Łukajtis
authors.forename: M
authors.initials: M
authors.lastname: Filipowicz
authors.forename: P
authors.initials: P
authors.lastname: Strzelecka
authors.forename: M
authors.initials: M
authors.lastname: Wysocka
authors.forename: A
authors.initials: A
authors.lastname: Łęgowska
authors.forename: A
authors.initials: A
authors.lastname: Lesner
authors.forename: K
authors.initials: K
authors.lastname: Rolka
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D034444:Peptoids; D014357:Trypsin / Q000737:chemistry; D014361:Trypsin Inhibitors / Q000737:chemistry; D015091:beta-Alanine
chemical_list: D000596:Amino Acids; D034444:Peptoids; D014361:Trypsin Inhibitors; D015091:beta-Alanine; D014357:Trypsin