Synthesis, kinetic characterization and X-ray analysis of peptide aldehydes as inhibitors of the 20S proteasomes from Thermoplasma acidophilum and Saccharomyces cerevisiae.
A comparative kinetic characterization of the peptide aldehydes Ac-Leu-Leu-X-H [X = Trp, Tyr and Tyr(tBu)] and Z-Gly-Pro-Gly-Gly-Leu-Leu-Nle-H as inhibitors of the chymotryptic activity of 20S proteasomes from the archaebacterium T. acidophilum and yeast S. cerevisiae revealed significantly differentiated inhibitory potencies that can be rationalized on the basis of X-ray crystallographic data.
Escherich
A
A
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Ditzel
L
L
Musiol
H J
HJ
Groll
M
M
Huber
R
R
Moroder
L
L
D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry; D002154:Calpain / Q000037:antagonists & inhibitors; D002918:Chymotrypsin; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013822:Thermoplasma / Q000737:chemistry / Q000378:metabolism*
D000447:Aldehydes; D009097:Multienzyme Complexes; D010455:Peptides; D002918:Chymotrypsin; D002154:Calpain; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex