Although proteases are capable of synthesizing peptide bonds, they are not proficient at peptide fragment ligation. Further manipulations are needed to shift the native enzyme activity from the cleavage to the synthesis of peptides. This account reports on the synthetic potential of nonactivatable trypsinogen and zymogen-like enzymes designed to minimize proteolytic side reactions during peptide synthesis.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1021/jo026117i | DOI Listing |
J Thromb Haemost
July 2023
Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada. Electronic address:
Background: ADAMTS13 is a circulating metalloprotease that cleaves von Willebrand factor (VWF) in a shear-dependent manner. ADAMTS13 is secreted as an active protease but has a long half-life, suggesting that it is resistant to circulating protease inhibitors. These zymogen-like properties indicate that ADAMTS13 exists as a latent protease that is activated by its substrate.
View Article and Find Full Text PDFJ Enzyme Inhib Med Chem
December 2022
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
Cathepsin K (CatK) is a target for the treatment of osteoporosis, arthritis, and bone metastasis. Peptidomimetics with a cyanohydrazide warhead represent a new class of highly potent CatK inhibitors; however, their binding mechanism is unknown. We investigated two model cyanohydrazide inhibitors with differently positioned warheads: an azadipeptide nitrile and a 3-cyano-3-aza-β-amino acid .
View Article and Find Full Text PDFBiomolecules
April 2021
Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology, University of Copenhagen, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark.
The vast majority of coagulation factor VII (FVII), a trypsin-like protease, circulates as the inactive zymogen. Activated FVII (FVIIa) is formed upon proteolytic activation of FVII, where it remains in a zymogen-like state and it is fully activated only when bound to tissue factor (TF). The catalytic domains of trypsin-like proteases adopt strikingly similar structures in their fully active forms.
View Article and Find Full Text PDFJ Thromb Haemost
June 2021
Department of Molecular and Cellular Hemostasis, Sanquin Research, Amsterdam, The Netherlands.
Background: Activated factor IX (FIXa) is an inefficient enzyme that needs activated factor VIII (FVIII) for full activity. Recently, we identified a network of FVIII-driven changes in FIXa employing hydrogen-deuterium eXchange mass spectrometry (HDX-MS). Some changes also occurred in active-site inhibited FIXa, but others were not cofactor-driven, in particular those within the 220-loop (in chymotrypsin numbering).
View Article and Find Full Text PDFJ Biol Chem
June 2020
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri, USA
The conformational properties of trypsin-like proteases and their zymogen forms remain controversial because of a lack of sufficient information on their free forms. Specifically, it is unclear whether the free protease is zymogen-like and shifts to its mature form upon a ligand-induced fit or exists in multiple conformations in equilibrium from which the ligand selects the optimal fit via conformational selection. Here we report the results of F NMR measurements that reveal the conformational properties of a protease and its zymogen precursor in the free form.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!