Development of lipopeptides for inhibiting 20S proteasomes.
Proteasomes are responsible for the cytoplasmic turnover of the vast majority of proteins including regulatory proteins. We have synthesized lipopeptides a new class of non-covalent inhibitors of the 20S proteasome and assayed their inhibitory capacities. Their ability to inhibit at micromolar concentrations chymotrypsin-like and post-acid activities depends on peptide length (3 or 6 amino acids), sequence (presence of a positively or negatively charged amino acid), and alkyl chain length (C6-C18). These structural features could be varied to selectively inhibit one or more of the three proteasome activities.
Basse
Nicolas
N
Laboratoire d'Enzymologie Moléculaire et Fonctionnelle, FRE2852, CNRS-Université Paris VI, Institut Jacques Monod, T43, 2 Place Jussieu, 75251 Paris Cedex 05, France.
Papapostolou
David
D
Pagano
Maurice
M
Reboud-Ravaux
Michèle
M
Bernard
Elise
E
Felten
Anne-Sophie
AS
Vanderesse
Régis
R
D000595:Amino Acid Sequence; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008074:Lipoproteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D010447:Peptide Hydrolases / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D008074:Lipoproteins; D010455:Peptides; D061988:Proteasome Inhibitors; C011545:semen liquefaction factor; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex