N alpha-formyl-norleucyl-leucyl-phenylalanyl chloromethylketone. A possible covalent agonist of the N alpha-formyl-methionyl-peptide receptor.
N alpha-formyl-norleucyl-leucyl-phenylalanine-chloromethyl ketone is chemotactic for, and induces lysosomal enzyme release from rabbit peritoneal neutrophils over essentially the same range of concentrations as does the free acid form of the same peptide (N alpha-formyl-norleucyl-leucyl-phenylalanine-OH). The chloromethyl ketone derivative does however differ from the free acid in respect to its ability to interact with the neutrophil and cause deactivation or desensitization to cytochalasin B. Neutrophils preincubated in the cold with the chloromethyl ketone followed by washing have cytochalasin B sensitivity conferred upon them, as measured by the release of lysosomal enzymes. The degree of release induced by this pre-treatment appears to be related to the initial responsiveness of the cells. This is in contrast to the free acid where no cytochalasin B sensitivity is conferred under any circumstances. Thus, the chloromethyl ketone, unlike the free acid, appears to irreversibly activate the cell. Desensitization to the late addition of cytochalasin B is also significantly retarded when the chloromethyl ketone derivative is compared to the free acid form of the peptide. These studies suggest that the chloromethyl ketone derivative of the peptide may covalently interact with the neutrophil receptor.
D000590:Amino Acid Chloromethyl Ketones / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002630:Chemotactic Factors / Q000494:pharmacology*; D003571:Cytochalasin B / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism*; D044042:Receptors, Formyl Peptide
D000590:Amino Acid Chloromethyl Ketones; D002630:Chemotactic Factors; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D003571:Cytochalasin B; C024998:N-formylnorleucyl-leucyl-4-phenylalanine; C033481:N-formylnorleucyl-leucyl-phenylalanine chloromethyl ketone