Design, synthesis and biological assay of novel tripeptidic tetrazoles as inhibitors of 20S proteasome

Ubiquitin-proteasome pathway (UPP) is one of the ways utilized for selective degradation of many proteins in cells, and the 20S proteasome takes the functional machinery where hydrolysis of targeted proteins takes place.  Based on existing peptide inhibitors, a series of novel tripeptidic tetrazoles have been designed, synthesized, and the structures have been confirmed with ¹H NMR, MS and elemental analysis.  Among them, three compounds (6b, 6d and 6h) showed inhibitory activities of ChT-L of 20S proteasome.