Novel fluorinated pseudopeptides as proteasome inhibitors.
We have designed novel small inhibitors of rabbit 20S proteasome using a trifluoromethyl-beta-hydrazino acid scaffold. Structural variations influenced their inhibition of the three types of active sites. Proteasome inhibition at the micromolar level was selective, calpain I and cathepsin B were not inhibited.
Formicola
Lucia
L
Faculté de Pharmacie, Université Paris-Sud 11, UMR-CNRS 8076, Molécules Fluorées et Chimie Médicinale, IFR 141, Châtenay-Malabry cedex, France.
Maréchal
Xavier
X
Basse
Nicolas
N
Bouvier-Durand
Michelle
M
Bonnet-Delpon
Danièle
D
Milcent
Thierry
T
Reboud-Ravaux
Michèle
M
Ongeri
Sandrine
S
D000818:Animals; D020134:Catalytic Domain; D005461:Fluorine; D005998:Glycine / Q000031:analogs & derivatives; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D061988:Proteasome Inhibitors; D011817:Rabbits; D013329:Structure-Activity Relationship
D010455:Peptides; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D005461:Fluorine; D005998:Glycine