Isolation and structure elucidation of two new calpain inhibitors from Streptomyces griseus.
Two new peptides, a diketopiperazine of N-methyltyrosine (1) and a tetrapeptide containing N-methyltyrosine (2), were isolated from an actinomycete strain Streptomyces griseus. These compounds inhibit the enzyme calpain in the micromolar range and were characterized on the basis of spectroscopic analysis, amino acid analysis and sequencing. The structure of the tetrapeptide N-methyltyrosyl-N-methyltyrosyl-leucyl-alanine (2), was also confirmed by total synthesis.
Alvarez
M E
ME
Sterling Winthrop Pharmaceutical Research Division, Malvern, PA 19355.
Houck
D R
DR
White
C B
CB
Brownell
J E
JE
Bobko
M A
MA
Rodger
C A
CA
Stawicki
M B
MB
Sun
H H
HH
Gillum
A M
AM
Cooper
R
R
D002154:Calpain / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013305:Streptomyces griseus / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
C091113:3,6-bis(4-hydroxyphenylmethyl)-1,4-dimethyl-2,5-diketopiperazine; D004791:Enzyme Inhibitors; C091112:N-methyltyrosyl-N-methyltyrosyl-leucyl-alanine; D009842:Oligopeptides; D010879:Piperazines; D014443:Tyrosine; D002154:Calpain