80640-15-9Relevant articles and documents
Approaching an experimental electron density model of the biologically active trans-epoxysuccinyl amide group—Substituent effects vs. crystal packing
Shi, Ming W.,Stewart, Scott G.,Sobolev, Alexandre N.,Dittrich, Birger,Schirmeister, Tanja,Luger, Peter,Hesse, Malte,Chen, Yu-Sheng,Spackman, Peter R.,Spackman, Mark A.,Grabowsky, Simon
supporting information, (2017/10/17)
The trans-epoxysuccinyl amide group as a biologically active moiety in cysteine protease inhibitors such as loxistatin acid E64c has been used as a benchmark system for theoretical studies of environmental effects on the electron density of small active i
Design, synthesis, and optimization of novel epoxide incorporating peptidomimetics as selective calpain inhibitors
Schiefer, Isaac T.,Tapadar, Subhasish,Litosh, Vladislav,Siklos, Marton,Scism, Rob,Wijewickrama, Gihani T.,Chandrasena, Esala P.,Sinha, Vaishali,Tavassoli, Ehsan,Brunsteiner, Michael,Fa', Mauro,Arancio, Ottavio,Petukhov, Pavel,Thatcher, Gregory R. J.
supporting information, p. 6054 - 6068 (2013/09/02)
Hyperactivation of the calcium-dependent cysteine protease calpain 1 (Cal1) is implicated as a primary or secondary pathological event in a wide range of illnesses and in neurodegenerative states, including Alzheimer's disease (AD). E-64 is an epoxide-containing natural product identified as a potent nonselective, calpain inhibitor, with demonstrated efficacy in animal models of AD. By use of E-64 as a lead, three successive generations of calpain inhibitors were developed using computationally assisted design to increase selectivity for Cal1. First generation analogues were potent inhibitors, effecting covalent modification of recombinant Cal1 catalytic domain (Cal1cat), demonstrated using LC-MS/MS. Refinement yielded second generation inhibitors with improved selectivity. Further library expansion and ligand refinement gave three Cal1 inhibitors, one of which was designed as an activity-based protein profiling probe. These were determined to be irreversible and selective inhibitors by kinetics studies comparing full length Cal1 with the general cysteine protease papain.
First asymmetric total synthesis of synerazol, an antifungal antibiotic, and determination of its absolute stereochemistry
Hayashi, Yujiro,Shoji, Mitsuru,Mukaiyama, Takasuke,Gotoh, Hiroaki,Yamaguchi, Shinpei,Nakata, Munetaka,Kakeya, Hideaki,Osada, Hiroyuki
, p. 5643 - 5654 (2007/10/03)
By synthesizing two possible diastereomers, the first asymmetric total synthesis of synerazol, an antifungal antibiotic, has been accomplished, allowing determination of its absolute stereochemistry. A more practical second generation route was also estab
