Lactacystin


Lactacystin is an organic compound naturally synthesized by bacteria of the genus Streptomyces first identified as an inducer of neuritogenesis in neuroblastoma cells in 1991. The target of lactacystin was subsequently to be to the proteasome on the basis for its affinity to certain catalytic subunits of the proteasome by Fenteany and co-workers in 1995. The proteasome is a protein complex responsible for the bulk of proteolysis in the cell, as well as proteolytic activation of certain protein substrates. It was the first non-peptidic proteasome inhibitor discovered and is widely used as a research tool in biochemistry and cell biology. It covalently modifies the amino-terminal threonine of specific catalytic subunits of the proteasome, a discovery helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal threonine protease. The molecule is most commonly used as in biochemistry and cell biology laboratories as a selective inhibitor of the proteasome. The first total synthesis of lactacystin was developed in 1992 by Corey and Reichard, and a number of other syntheses of this molecule have also been published. There are more than 1,660 entries for lactacystin in PubMed as of January 2019.