56361-75-2Relevant academic research and scientific papers
Biosynthetic reconstitution of deoxysugar phosphoramidate metalloprotease inhibitors using an N-P-bond-forming kinase
Baulig, Alexandra,Helmle, Irina,Bader, Marius,Wolf, Felix,Kulik, Andreas,Al-Dilaimi, Arwa,Wibberg, Daniel,Kalinowski, J?rn,Gross, Harald,Kaysser, Leonard
, p. 4486 - 4490 (2019/04/29)
Phosphoramidon is a potent metalloprotease inhibitor and a widespread tool in cell biology research. It contains a dipeptide backbone that is uniquely linked to a 6-deoxysugar via a phosphoramidate bridge. Herein, we report the identification of a gene cluster for the formation of phosphoramidon and its detailed characterization. In vitro reconstitution of the biosynthesis established TalE as a phosphoramidate-forming kinase and TalC as the glycosyltransferase which installs the l-rhamnose moiety by phosphoester linkage.
Effects of Metalloprotease Inhibitors on Smooth Muscle Endothelin-Converting Enzyme Activity
Balwierczak, Joseph L.,Kukkola, Paivi J.,Savage, Paula,Jeng, Arco Y.
, p. 291 - 296 (2007/10/03)
The enzyme responsible for the conversion of exogenous big endothelin-1 to endothelin-1 by porcine coronary arterial smooth muscle has been shown to be a metalloprotease. The potencies of eight metalloprotease inhibitors for this endothelin-converting enzyme were determined. CGS 25015, CGS 26129, and thiorphan inhibited the enzyme activity monophasically with IC50 values of 2.6, 2.4, and 190 μM, respectively. In contrast, the data obtained using phosphoramidon as an inhibitor were best fit by a two-site model. The biphasic concentration-response curve had IC50 values of 4.6 μM and 2.2 mM. Three analogs of phosphoramidon were also tested for enzyme inhibition. Removal of the rhamnose moiety of phosphoramidon reduced the potency (IC50=15 μM), whereas substitution of the rhamnose by N-[2-(2-naphthyl)ethyl] improved the potency (IC50=2.0 μM). These results identify a thiol and a phosphonyl series of compounds as smooth muscle endothelin-converting enzyme inhibitors. The structure-activity relationships revealed that an aromatic or aliphatic group in the P2' position or an aromatic group in the P1 position of the inhibitor significantly increased the potency.
