title: Introduction of Pro and its analogues in the conserved P1' position of trypsin inhibitor SFTI-1 retains its inhibitory activity.
abstract: 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.
authors: Faculty of Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdansk, Poland. legowska@chem.univ.gda.pl
authors: Anna
authors: A
authors: Łęgowska
authors: Dawid
authors: D
authors: Dębowski
authors: Rafał
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authors: Łukajtis
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authors: Sztabkowska
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authors: Mizeria
authors: Krzysztof
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