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.
Autorzy
- Anna Legowska,
- Dawid Debowski,
- Rafal Lukajtis,
- Emilia Sztabkowska,
- Aneta Mizeria,
- dr Krzysztof Brzozowski,
- Magdalena Wysocka,
- Adam Lesner link otwiera się w nowej karcie ,
- Krzysztof Rolka,
- Rafał Łukajtis link otwiera się w nowej karcie
Informacje dodatkowe
- DOI
- Cyfrowy identyfikator dokumentu elektronicznego link otwiera się w nowej karcie 10.2174/092986611797201002
- Kategoria
- Publikacja w czasopiśmie
- Typ
- artykuł w czasopiśmie wyróżnionym w JCR
- Język
- angielski
- Rok wydania
- 2011
