1252801-31-2Relevant academic research and scientific papers
Optimization of a series of dipeptides with a P3 β-neopentyl asparagine residue as non-covalent inhibitors of the chymotrypsin-like activity of human 20S proteasome
Blackburn, Christopher,Barrett, Cynthia,Blank, Jonathan L.,Bruzzese, Frank J.,Bump, Nancy,Dick, Lawrence R.,Fleming, Paul,Garcia, Khristofer,Hales, Paul,Jones, Matthew,Liu, Jane X.,Nagayoshi, Masayuki,Sappal, Darshan S.,Sintchak, Michael D.,Tsu, Christopher,Xia, Cindy,Zhou, Xiansi,Gigstad, Kenneth M.
, p. 710 - 719 (2013/11/06)
Inhibition of the proteasome by covalent inhibitors is a clinically proven anti-cancer therapy. We report here that dipeptides with a P3 neopentyl Asn residue are potent, reversible, non-covalent inhibitors selective for the chymotryptic activity of the 20S proteasome in vitro and in cells. The X-ray structure of compound 20 in complex with yeast 20S reveals the importance of hydrophobic bonding interactions of the neopentyl group within the S3 binding pocket of the 20S β5 sub-unit. Four compounds show comparable potencies to boronic acid inhibitors in a panel of assays.
Characterization of a new series of non-covalent proteasome inhibitors with exquisite potency and selectivity for the 20S β5-subunit
Blackburn, Christopher,Gigstad, Kenneth M.,Hales, Paul,Garcia, Khristofer,Jones, Matthew,Bruzzese, Frank J.,Barrett, Cynthia,Liu, Jane X.,Soucy, Teresa A.,Sappal, Darshan S.,Bump, Nancy,Olhava, Edward J.,Fleming, Paul,Dick, Lawrence R.,Tsu, Christopher,Sintchak, Michael D.,Blank, Jonathan L.
scheme or table, p. 461 - 476 (2012/05/05)
The mammalian 26S proteasome is a 2500 kDa multi-catalytic complex involved in intracellular protein degradation. We describe the synthesis and properties of a novel series of non-covalent di-peptide inhibitors of the proteasome used on a capped tri-pepti
