Patent ID: 6838477

Claim:
A method for identifying a biological process mediated by proteasome-dependent proteolysis, said method comprising: contacting a cell preparation or cell extract with a compound of formula wherein Z 1 is O, S, SO 2 , NH, or NR a , R a being C 1-6 alkyl; X 1 is O, S, CH 2 , two singly bonded H, CH(R b ) in the E or Z configuration, or C(R b )(R c ) in the E or Z configuration, each of R b and R c , independently, being C 1-6 alkyl, C 6-12 aryl, C 3-8 cycloalkyl, C 3-8 heteroaryl, C 3-8 heterocyclic radical, or halogen, provided that when Z 1 is SO 2 , X 1 is two singly bonded H; Z 2 is CHR 1 in the (R) or (S) configuration, R 1 being H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxyl, halogen, a side chain of a naturally occurring α-amino acid, OR d , SR d , or NR d R e , each of R d and R e , independently, being H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, or C 2-5 alkynyl; Z 3 is O, S, NH, or NR j , wherein R j is C 1-6 alkyl; X 2 is O or S; and A 1 is H, the side chain of any naturally occurring α-amino acid, or is of the following formula, —(CH 2 ) m —Y(CH 2 ) n —R 3 X 3 wherein Y is O, S, C═O, C═S, —(CH═CH)—, vinylidene, —C═NOR h , —C═NNR i R i′ , sulfonyl, methylene, CHX 4 in the (R) or (S) configuration, or deleted, X 4 being halogen, methyl, halomethyl, OR h , SR h , NR i R i′ , —NR i (OR h ), or —NR i (NR i R i′ ), wherein R h is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, and each of R i and R i′ , independently is selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-10 acyl; m is 0, 1, 2, or 3, and n is 0, 1, 2, or 3; and R 3 is straight chain or branched C 1-8 alkylidene, straight chain or branched C 1-8 alkylene, C 3-10 cycloalkylidene, C 3-10 cycloalkylene, phenylene, C 6-14 arylalkylidene, C 6-14 arylalkylene, or deleted, and X 3 is H, hydroxyl, thiol, carboxyl, amino, halogen, (C 1-6 alkyl) oxycarbonyl, (C 7-14 arylalkyl)-oxycarbonyl, or C 6-14 aryl; or R 3 and X 3 taken together are the side chain of any naturally occurring α-amino acid; and measuring an effect of said compound on a biological process; wherein the measurement of the effect indicates that said biological process is mediated by proteasome-dependent proteolysis.