Reference

Analogs of chymostatin

Analogs of chymostatin. Galpin, Ian J.; Wilby, Anna H.In this study， 88191-84-8 and 9004-07-3 are also used.; Beynon, Robert J. (Dep. Org. Chem., Univ. Liverpool, Liverpool L69 3BX, UK). Pept., Proc. Eur. Pept. Symp., 17th, Meeting Date 1982, 649-52. Edited by: Blaha, Karel; Malon, Petr. de Gruyter: Berlin, Fed. Rep. Ger. (English) 1983. CODEN: 50GFAA. DOCUMENT TYPE: Conference CA Section: 7 (Enzymes) A series of peptide aldehydes of the general structure Z-Arg-X-Phe-H (Z = benzyloxycarbonyl; X = leucine, isoleucine, or valine) and their resp. semicarbazones was prepd. and tested as chymostatin analogs. The peptide aldehydes were prepd. from phenylalanine aldehyde semicarbazone p-toluenesulfonate by peptide coupling methods. When detd. as the inhibition of chymotryptic hydrolysis of Glu-Phe-7-amino-4-methylcoumarin or as the displacement of ligand from proflavin-chymotrypsin complexes, analogs with X = leucine were most potent. .

The calpain inhibitor MDL 28170 prevents inflammation-induced neurofilament light chain breakdown in the spinal cord and reduces thermal hyperalgesia

The calpain inhibitor MDL 28170 prevents inflammation-induced neurofilament light chain breakdown in the spinal cord and reduces thermal hyperalgesia. Kunz, Susanne; Niederberger, Ellen; Ehnert, Corina; Coste, Ovidiu; Pfenninger, Anja; Kruip, Jochen; Wendrich, Thomas M.; Schmidtko, Achim; Tegeder, Irmgard; Geisslinger, Gerd (Institut fur Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universitaet, Frankfurt am Main 60590, Germany). Pain, 110(1-2), 409-418 (English) 2004 Elsevier Ltd. CODEN: PAINDB. ISSN: 0304-3959. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Since long-term hyperexcitability of nociceptive neurons in the spinal cord has been suggested to be caused and maintained by changes of protein expression we assessed protein patterns in lumbar spinal cord during a zymosan induced paw inflammation employing two-dimensional (2D) gel electrophoresis. 2D PAGE revealed a time-dependent breakdown of scaffolding proteins one of which was neurofilament light chain (NFL) protein, which has been previously important for axonal architecture and transport. Nociception induced breakdown of NFL in the spinal cord and dorsal root ganglias was prevented by pretreatment of the animals with a single dose of the specific inhibitor of the protease calpain (MDL-28170) which has been shown to be the primary protease involved in neurofilament degrdn. in neurodegenerative diseases. Treatment with the calpain inhibitor also provided anti-inflammatory and anti-hyperalgesic effects in the zymosan-induced paw inflammation model irresp. of whether the drug was administered systemically (i.p.) or delivered onto the lumbar spinal cord. This suggests that the activation of calpain is involved in the sensitization of nociceptive neurons what is partly due to neurofilament breakdown but cleavage of other calpain substrates may also be involved. Our results indicate that inhibition of pathol.In this experiment, several chemicals are used like 78990-62-2 and 88191-84-8 calpain activity may present an interesting novel drug target in the treatment of pain and inflammation. .