P3 and P4 position analysis of vinyl ester pseudopeptide proteasome inhibitors.
Two small libraries of tripeptidic-based vinyl ester derivative proteasome inhibitors were synthesized and tested, starting with the Hmb-Val-Gln-Leu-VE prototype. The P3 and P4 positions were investigated with a complete set of amino acid residues, some of which showed remarkable selective inhibition of the trypsin-like (beta2) subunit. In both positions, aromatic and hydrophobic residues were preferred.
Marastoni
Mauro
M
Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, I-44100 Ferrara, Italy. mru@dns.unife.it
Baldisserotto
Anna
A
Trapella
Claudio
C
Gavioli
Riccardo
R
Tomatis
Roberto
R
D000595:Amino Acid Sequence; D004952:Esters / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D014753:Vinyl Compounds / Q000737:chemistry*
D004952:Esters; D010455:Peptides; D061988:Proteasome Inhibitors; D014753:Vinyl Compounds; D046988:Proteasome Endopeptidase Complex