New chemotactic peptide analogs with high biological activity for human neutrophils.
As a part of a research programme aimed at studying structure activity relationships in the field of chemotactic peptides, modified analogs of the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) were examined for their capacity to activate several functions of human neutrophils. 4-Aminotetrahydrothiopyran-4carboxylic acid (Thp) and 2-aminoindane-2-carboxylic acid (Ain) were chosen as achiral, conformationally restricted amino acids suitable for mimicking the external Met and Phe residues of FMLP-OMe. The replacement of both produces a high locomotion activity, greater than the parent peptide; in contrast, the two Thp-containing analogs induce neither superoxide production nor lysozyme release. From these results we can hypothesize two different signal transduction systems: one which provides for movement, the other for superoxide generation and granule enzyme release.
Spisani
S
S
Istituto di Chimica Biologica, Università degli Studi di Ferrara, Italy.
Traniello
S
S
Giuliani
A L
AL
Torrini
I
I
Pagani Zecchini
G
G
Paglialunga Paradisi
M
M
Gavuzzo
E
E
Mazza
F
F
Pochetti
G
G
Lucente
G
G
D000595:Amino Acid Sequence; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011487:Protein Conformation; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009113:Muramidase