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Journal articles
Structure-based design of human immuno- and constitutive proteasomes inhibitors
Abstract : Starting from the X-ray structure of our previous tripeptidic linear mimics of TMC-95A in complex with yeast 20S proteasome, we introduced new structural features to induce a differential inhibition between human constitutive and immunoproteasome 20S particles. Libraries of 24 tripeptidic and 6 dipeptidic derivatives were synthesized. The optimized preparation of 3-hydroxyoxindolyl alanine residues from tryptophan and their incorporation in peptides were described. Several potent inhibitors of human constitutive proteasome and immunoproteasome acting at the nanomolar level (IC50 = 7.1 nM against the chymotrypsin-like activity for the best inhibitor) were obtained. A cytotoxic effect at the submicromolar level was observed against 6 human cancer cell lines.
Cited literature [73 references]
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01713510
Contributor : Laurent Jonchère <>
Submitted on : Wednesday, April 25, 2018 - 2:54:19 PM
Last modification on : Thursday, July 30, 2020 - 3:11:55 AM
Long-term archiving on: : Tuesday, September 25, 2018 - 1:13:00 PM
Contributor : Laurent Jonchère <>
Submitted on : Wednesday, April 25, 2018 - 2:54:19 PM
Last modification on : Thursday, July 30, 2020 - 3:11:55 AM
Long-term archiving on: : Tuesday, September 25, 2018 - 1:13:00 PM
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