Properties of a novel chemotactic esapeptide, an analogue of the prototypical N-formylmethionyl peptide.
The new disulphur-bridged peptide, for-Met-Leu-Cys(OMe)-Cys(OMe)-Leu-Met-for, has been synthesized and its biological properties resulting from its binding to the formyl-peptide receptor of human neutrophils characterized. Three activities resulting from this interaction were measured: directed cell migration (i.e., chemotaxis); superoxide anion production; and lysozyme enzyme release. The properties were compared with those observed for the prototypical peptide, for-Met-Leu-Phe-OMe. Chemotaxis is strongly triggered while both superoxide anion production and lysosomal enzyme release are elicited only at high concentrations and never reach the response peak observed for the prototype peptide at physiologically relevant concentrations. The derivative appears to bind with a good affinity to the formyl-peptide receptors. These results provide new information regarding the structure-activity relationship of the formyl-peptide receptor.
Cavicchioni
Giorgio
G
Department of Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara 17/19, 44100, Ferrara, Italy. g5z@dns.unife.it
Turchetti
Marianna
M
Varani
Katia
K
Falzarano
Sofia
S
Spisani
Susanna
S
D002633:Chemotaxis / Q000187:drug effects*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014316:Tritium
D014316:Tritium; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester