Łęgowska Anna, Dębowski Dawid, Łukajtis Rafał, Sztabkowska Emilia, Mizeria Aneta, Brzozowski Krzysztof, Wysocka Magdalena, Lesner Adam, Rolka Krzysztof
Faculty of Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdansk, Poland.
Protein Pept Lett. 2011 Nov;18(11):1158-67. doi: 10.2174/092986611797201002.
A number of monocyclic SFTI-1 analogues modified in the conserved inhibitor P1' position by Pro, its L-hydroxyproline (Hyp) derivative as well as mimetics with different ring size were synthesized by the solid-phase method. Replacement of Ser6 by Pro, Hyp, and a four-member ring, L-azetidine-2-carboxylic acid (Aze), retained trypsin or chymotrypsin inhibitory activity. The determined association equilibrium constants of these analogues with a cognate enzyme were about two orders of magnitude lower than those obtained for ones with conserved Ser6. In all analogues, with the exception of one, [Phe5,Aze6]SFTI-1, the P1-P1' reactive site remained intact. The results provide first evidence that the conserved Ser in the P1' position of Bowman-Birk inhibitors can be successfully replaced by an amino acid with a secondary amine group.
