Search results for "Tiopronin"
showing 4 items of 4 documents
Proteomic Analyses Reveal an Acidic Prime Side Specificity for the Astacin Metalloprotease Family Reflected by Physiological Substrates
2011
Astacins are secreted and membrane-bound metalloproteases with clear associations to many important pathological and physiological processes. Yet with only a few substrates described their biological roles are enigmatic. Moreover, the lack of knowledge of astacin cleavage site specificities hampers assay and drug development. Using PICS (proteomic identification of protease cleavage site specificity) and TAILS (terminal amine isotopic labeling of substrates) degradomics approaches >3000 cleavage sites were proteomically identified for five different astacins. Such broad coverage enables family-wide determination of specificities N- and C-terminal to the scissile peptide bond. Remarkably, me…
Meprins process matrix metalloproteinase-9 (MMP-9)/gelatinase B and enhance the activation kinetics by MMP-3
2012
Abstract Meprin α and β, members of the astacin family of zinc metalloproteinases, are unique plasma membrane and secreted proteases known to cleave a wide range of biological substrates involved in inflammation, cancer and fibrosis. In this study, we identified proMMP-9 as a novel substrate and show that aminoterminal meprin-mediated clipping improves the activation kinetics of proMMP-9 by MMP-3, an efficient activator of proMMP-9. Interestingly, the NH2-terminus LVLFPGDL, generated by incubation with meprin α, is identical to the form produced in conditioned media from human neutrophils and monocytes. Hence, this meprin-mediated processing and enhancement of MMP-9 activation kinetics may …
Chromatographic Determination of Thiols After Pre‐column Derivatization witho‐Phthalaldehyde and Isoleucine
2004
Abstract The reaction of primary amines with excess o‐phthalaldehyde (OPA) and thiol yields unique isoindole derivatives that are readily separated by reversed‐phase liquid chromatography. In a previous work, a spectrophotometric procedure was proposed for the assay of N‐acetylcysteine by derivatization with OPA and isoleucine at pH 9.5, with satisfactory results. The chromatographic determination of this and other low molecular‐weight thiols, after isoindole formation with isoleucine, using mobile phases of acetonitrile–water at pH 3 and spectrophotometric detection, is now examined. From the assayed thiols (thioglycolic acid, 3‐mercaptopropionic acid, tiopronin, N‐acetylcysteine, N‐acetyl…
Metalloprotease meprin beta generates nontoxic N-terminal amyloid precursor protein fragments in vivo.
2011
Identification of physiologically relevant substrates is still the most challenging part in protease research for understanding the biological activity of these enzymes. The zinc-dependent metalloprotease meprin β is known to be expressed in many tissues with functions in health and disease. Here, we demonstrate unique interactions between meprin β and the amyloid precursor protein (APP). Although APP is intensively studied as a ubiquitously expressed cell surface protein, which is involved in Alzheimer disease, its precise physiological role and relevance remain elusive. Based on a novel proteomics technique termed terminal amine isotopic labeling of substrates (TAILS), APP was identified …