Probing structural requirements of fMLP receptor: on the size of the hydrophobic pocket corresponding to residue 2 of the tripeptide.
The conformationally constrained f-L-Met-Ac(n)c-L-Phe-OMe (n = 4,9-12) tripeptides, analogues of the chemoattractant f-L-Met-L-Leu-L-Phe-OH, were synthesized in solution by classical methods and fully characterized. These compounds and the published f-L-Met-Xxx-L-Phe-OMe (Xxx = Aib and Ac(n)c where n = 3, 5-8) analogues were compared to determine the combined effect of backbone preferred conformation and side-chain bulkiness at position 2 on the relation of 3D-structure to biological activity. A conformational study of all the analogues was performed in solution by FT-IR absorption and 1H-NMR techniques. In parallel, each peptide was tested for its ability to induce chemotaxis, superoxide anion production and lysozyme secretion from human neutrophils. The biological and conformational data are discussed in relation to the proposed model of the chemotactic receptor on neutrophils, in particular of the hydrophobic pocket accommodating residue 2 of the tripeptide.
Spisani
Susanna
S
Department of Biochemistry and Molecular Biology, University of Ferrara, Italy.
Traniello
Serena
S
Cavicchioni
Giorgio
G
Formaggio
Fernando
F
Crisma
Marco
M
Toniolo
Claudio
C
D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000737:chemistry; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009504:Neutrophils / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000737:chemistry*; D018000:Receptors, Peptide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013481:Superoxides
D008024:Ligands; D010455:Peptides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D013481:Superoxides; D010100:Oxygen; D005998:Glycine