Search results for "Cathepsin C"
showing 6 items of 16 documents
Pentapeptides containing two dehydrophenylalanine residues - synthesis, structural studies and evaluation of their activity towards cathepsin C
2008
Synthesis, structural and biological studies of pentapeptides containing two Delta Phe residues (Z and E isomers) in position 2 and 4 in peptide chain were performed. All the investigated peptides adopted bent conformation and majority of them could exist as two different. conformers in solution. Only pentapeptides. containing free N-termini appeared to act as weak inhibitors of cathepsin C with the slow-binding, competitive mechanism of inhibition. free acids being bound slightly better than their methyl esters. Results of Molecular modeling suggested significant difference between peptides, depending of the type of amino acid residue in position 5 in peptide chain. Dehydropeptides contain…
Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C
2014
Mammalian cathepsin C is primarily responsible for the removal of N-terminal dipeptides and activation of several serine proteases in inflammatory or immune cells, while its malarial parasite ortholog dipeptidyl aminopeptidase 1 plays a crucial role in catabolizing the hemoglobin of its host erythrocyte. In this report, we describe the systematic substrate specificity analysis of three cathepsin C orthologs from Homo sapiens (human), Bos taurus (bovine) and Plasmodium falciparum (malaria parasite). Here, we present a new approach with a tailored fluorogenic substrate library designed and synthesized to probe the S1 and S2 pocket preferences of these enzymes with both natural and a broad ran…
Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C
2023
In this paper, we present the solvolysis reaction of dipeptide analogues of fluorinated aminophosphonates with simultaneous quantitative deprotection of the amino group. To the best of our knowledge, this work is the first reported example of the application of fluorinated aminophosphonates in cathepsin C inhibition studies. The new molecules show moderate inhibition of the cathepsin C enzyme, which opens the door to consider them as potential therapeutic agents. Overall, our findings provide a new avenue for the development of fluorinated aminophosphonate-based inhibitors. This article is part of the thematic issue "Organophosphorus chemistry: from model to application".
Peptide p-nitrophenylanilides containing (E)-dehydrophenylalanine—synthesis, structural studies and evaluation of their activity towards cathepsin C
2006
Tetrapeptide p-nitroanilides containing (E)-dehydrophenylalanine were synthesized and evaluated as inhibitors and substrates of cathepsin C. Peptides containing a free, unblocked amino group appeared to be quite good substrates of the enzyme, whereas fully protected peptides acted as very weak inhibitors. Structural studies by means of NMR and CD, alongside with molecular modelling, have proved that these peptides are hydrolysed in one step by direct removal of p-nitroaniline from the tetrapeptide.
Synthesis of dehydrodipeptide esters and their evaluation as inhibitors of cathepsin C
2015
The procedures for the synthesis of esters of dehydropeptides containing C-terminal (Z)-dehydrophenylalanine and dehydroalanine have been elaborated. These esters appeared to be moderate or weak inhibitors of cathepsin C, with some of them exhibiting slow-binding behavior. As shown by molecular modeling, they are rather bound at the surface of the enzyme and are not submersed in its binding cavities. Electronic supplementary material The online version of this article (doi:10.1007/s00044-015-1366-0) contains supplementary material, which is available to authorized users.
Synthesis of Hybrid Tripeptide Peptidomimetics Containing Dehydroamino Acid and Aminophosphonic Acid in the Chain and Evaluation of Their Activity to…
2021
Synthesis of a new group of hybrid phosphonodehydropeptides composed of glycyl-(Z)-dehydrophenylalanine and structurally variable aminophosphonates alongside with investigations of their activity towards cathepsin C are presented. Obtained results suggest that the introduction of (Z)- dehydrophenylalanine residue into the short phosphonopeptide chain does induce the ordered conformation. Investigated peptides appeared to act as weak or moderate inhibitors of cathepsin C.