Peptidyl vinyl ester derivatives: new class of selective inhibitors of proteasome trypsin-like activity.
The proteasome is a multicatalytic proteinase complex which plays a central role in intracellular protein degradation. We report here the synthesis and biological activities of a new class of specific proteasome inhibitors selective for trypsin-like activity. These tripeptide-based compounds bearing a C-terminal vinyl ester are nontoxic, and do not affect cell proliferation, but are able to modulate the generation and presentation of immunogenic peptides presented by MHC class I molecules.
Marastoni
Mauro
M
Department of Pharmaceutical Sciences and Biotechnology Centre, University of Ferrara, I-44100 Ferrara, Italy. mru@unife.it
Baldisserotto
Anna
A
Cellini
Silvia
S
Gavioli
Riccardo
R
Tomatis
Roberto
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000939:Epitopes; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015789:HLA-A2 Antigen / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014361:Trypsin Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D000939:Epitopes; D004952:Esters; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D014361:Trypsin Inhibitors; D014753:Vinyl Compounds