Literature

Abstract

Tyropeptin A, a new potent proteasome inhibitor, was produced by Kitasatospora sp. MK993-dF2. To enhance the inhibitory potency of tyropeptin A, we constructed the structural model of tyropeptin A bound to the site responsible for the chymotrypsin-like activity of mammalian 20S proteasome. Based on these modeling experiments, we designed and synthesized several derivatives of tyropeptin A. Among them, the most potent compound, TP-104, exhibited a 20-fold enhancement in its inhibitory potency compared to tyropeptin A. Additionally, TP-110 specifically inhibited the chymotrypsin-like activity, but did not inhibit the PGPH and the trypsin-like activities.

DOI： 10.1016/j.bmcl.2005.02.013

Structure-based design of derivatives of tyropeptin A as the potent and selective inhibitors of mammalian 20S proteasome

Bioorganic & Medicinal Chemistry Letters 2005.0

Tyropeptins A and B, New Proteasome Inhibitors Produced by Kitasatospora sp. MK993-dF2. I. Taxonomy, Isolation, Physico-chemical Properties and Biological Activities.

The Journal of Antibiotics 2001.0

C1 and N5 derivatives of cerpegin: Synthesis of a new series based on structure–activity relationships to optimize their inhibitory effect on 20S proteasome

Bioorganic & Medicinal Chemistry Letters 2013.0

A new series of N5 derivatives of the 1,1,5-trimethyl furo[3,4-c]pyridine-3,4-dione (cerpegin) selectively inhibits the post-acid activity of mammalian 20S proteasomes

Bioorganic & Medicinal Chemistry Letters 2012.0

New betulinic acid derivatives as potent proteasome inhibitors

Bioorganic & Medicinal Chemistry Letters 2011.0

New C4- and C1-derivatives of furo[3,4-c]pyridine-3-ones and related compounds: Evidence for site-specific inhibition of the constitutive proteasome and its immunoisoform