Elucidation of the a-Keto-Aldehyde Binding Mechanism: A Lead Structure Motif for Proteasome Inhibition

Angewandte Chemie, 2011, 50, 2, 542 - 44 published on 10.01.2011

Angewandte Chemie, online article

The proteasome's participation in essential biological processes such as stress response, cell proliferation, apoptosis, and antigen presentation has been well established.[1] It is, therefore, not surprising that academia and the pharmaceutical industry have made efforts to develop a range of small synthetic inhibitors against this proteolytic molecular machine (see Scheme SS1 in the Supporting Information for examples).[2] An overall structural comparison of some wellcharacterized inhibitors[3] implies that most of these compounds form a covalent bond with the N-terminal nucleophilic threonine (Thr1)[4] located at the active sites in the two inner heptameric b rings of the 20S proteasome, termed beta1, beta2, and beta5 according to the subunit of their origin.

Campus Movie 2020


Campus Movie 2012

TU München
Helmholtz München
MPI of Neurobiology
MPI of Biochemistry