Synthesis and biological evaluation of new vinyl ester pseudotripeptide proteasome inhibitors.
Here we report the synthesis and biological activities of new tripeptidic-based vinyl ester derivative proteasome inhibitors. Starting from Hmb-Val-Ser-Leu-VE prototype, we investigated P2 position and N-terminal substitution. The more effective inhibitors of the series showed remarkable inhibition and selectivity for the trypsin-like (beta2) subunit and were revealed to be specific for the proteasome. In vitro metabolic stability studies of the new vinyl ester analogues are also reported here.
Marastoni
M
M
Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, I-44100 Ferrara, Italy. mru@dns.unife.it
Baldisserotto
A
A
Trapella
C
C
Gavioli
R
R
Tomatis
R
R
D004353:Drug Evaluation, Preclinical; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D012680:Sensitivity and Specificity
D009842:Oligopeptides; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors