Analogues of trypsin inhibitor SFTI-1 with disulfide bridge substituted by various length of carbonyl bridges.

Series of eight new monocyclic analogues of trypsin inhibitor SFTI-1 was synthesized by the solid phase method. In these analogues disulfide bridge Cys3 - Cys11 present in native inhibitor was replaced by different-sized carbonyl bridges formed by the amino groups of the side chain of Lys, Orn, Dab or Dap located in positions 3 and/or 11. All analogues appeared to be potent trypsin inhibitors.

Inhibitory activity of double-sequence analogues of trypsin inhibitor SFTI-1 from sunflower seeds: an example of peptide splicing.

Four 28-amino acid peptides were synthesized whose sequences comprised two molecules of trypsin inhibitor sunflower trypsin inhibitor 1 (SFTI-1) bound through a peptide bond. The peptides in their reactive positions (5 and 19 of the peptide chain) contain two Lys ([KK]BiSFTI-1) and two Phe ([FF]BiSFTI-1) residues, along with a combination of the amino acid residues named thereafter [KF]BiSFTI-1 and [FK]BiSFTI-1. Association constants of the analogues determined with trypsin and chymotrypsin, respectively, indicated that they were potent inhibitors of cognate proteinases.

Peptomeric analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds.

A series of linear and monocyclic analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds, modified by N-(4-aminobutyl)glycine (Nlys) and N-benzylglycine (Nphe), were obtained by the solid-phase method. Some of these peptomers displayed trypsin or chymotrypsin inhibitory activity. In contradiction to the literature data, in most analogues peptide bonds formed by these peptoid monomers were at least partially hydrolyzed by the experimental enzymes at two different pH (3.

New chromogenic substrates of human neutrophil cathepsin G containing non-natural aromatic amino acid residues in position P(1) selected by combinatorial chemistry methods.

Specificity of human cathepsin G was explored using combinatorial chemistry methods. Deconvolution of a tetrapeptide library, where 5-amino-2-nitrobenzoic acid served as a chromophore attached at the C-terminus, yielded the active sequence Phe-Val-Thr-Tyr-Anb(5,2)-NH(2). This sequence was used for a second-generation library with the general formula Ac-Phe-Val-Thr-X-Anb(5,2)-NH(2), where position X was replaced with several amino acids: L-pyridyl- alanine (Pal), 4-nitro-L-phenylalanine (Nif), 4-amino-L- phenylalanine (Amf), 4-carboxy-L-phenylalanine (Cbf), 4-guanidine-L-phenylalanine (Gnf), 4-methyloxycarbonyl- L-phenylalanine (Mcf), 4-cyano-L-phenylalanine (Cyf), Phe, Tyr, Arg and Lys.