Hydrophilic residues at position 3 highlight unforeseen features of the fMLP receptor pocket.
The peptides for-Met-Leu-Tyr-OMe, for-Met-Leu-Glu-OMe, for-Met-Leu-Asp-OMe and for-Met-Leu-Ser-OMe were synthesized to investigate the importance of a hydrophilic side chain of the residue at position 3 on biological activities of human neutrophils. A number of in vitro essays were carried out, including: chemotaxis, superoxide anion production, lysozyme release and receptor binding. Our results highlight that for-Met-Leu-Asp-OMe acts as a full agonist with a higher efficacy than formyl-Met-Leu-Phe-OMe, the tripeptide normally used as a model chemoattractant for the study of cell functions. The other analogs show efficacies that are in the same range or a little less than the prototype. The main point emerging from this study is that the role of Phe substitution needs to be re-hypothesised.
Spisani
Susanna
S
Department of Biochemistry and Molecular Biology, University of Ferrara, Via L. Borsari 46, 44100 Ferrara, Italy.
Turchetti
Marianna
M
Varani
Katia
K
Falzarano
Sofia
S
Cavicchioni
Giorgio
G
D004305:Dose-Response Relationship, Drug; D006801:Humans; D009504:Neutrophils / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D044042:Receptors, Formyl Peptide / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D044042:Receptors, Formyl Peptide