The core structure of TMC-95A is a promising lead for reversible proteasome inhibition.

Abstract

Correspondingly,great attention has recently been paid to the discovery ofpotentandselectiveproteasomeinhibitorsbystructure-baseddesignornaturalproductscreeningapproaches.Mostofthesynthetic inhibitors consisting of peptide aldehydes, boro-nates, and vinylsulfones, as well as the natural productslactacystinandepoxymicinsinhibitinamoreorlessselectivemanner the proteasome by reaction with the N-terminalthreonineresidue(forarecentreviewseeref.[5]).Anotableexceptionisthehighlyselectiveandcompetitiveproteasomeinhibitor TMC-95A, which was isolated from the fermenta-tionbrothofApiosporamontagneiSacc.TC1093.