Isolation and structural determination of phepropeptins A, B, C, and D, new proteasome inhibitors, produced by Streptomyces sp.
We have isolated four related compounds named phepropeptins A, B, C, and D, as inhibitors of proteasome proposed to regulate many cellular functions. From an NMR analysis, the phepropeptins appeared as cyclic hexapeptides, differing in the two residues of the constituent amino acids from one another, with four conserved amino acid moieties. Based on an amino acid analysis, we synthesized two possible cyclic peptides to phepropeptin B that differ in the configurations. A comparison of the properties between the natural and synthesized compounds revealed that the structure of phepropeptin B was cyclo(-L-Leu-D-Phe-L-Pro-L-Phe-D-Leu-L-Val-). The phepropeptins showed inhibition to the proteasomal chymotrypsin-like activity but not to alpha-chymotrypsin.
Sekizawa
R
R
Institute of Microbial Chemistry, Tokyo, Japan. sekryu@bikaken.or.jp
Momose
I
I
Kinoshita
N
N
Naganawa
H
H
Hamada
M
M
Muraoka
Y
Y
Iinuma
H
H
Takeuchi
T
T
D000596:Amino Acids / Q000032:analysis; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D003546:Cysteine Endopeptidases; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D005285:Fermentation; D005470:Fluorometry; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009904:Optical Rotation; D010447:Peptide Hydrolases / Q000032:analysis; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D046988:Proteasome Endopeptidase Complex; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism*
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D010456:Peptides, Cyclic; C447404:phepropeptin A; C447407:phepropeptin B; C447406:phepropeptin C; C447405:phepropeptin D; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex