Modified chemotactic peptides: synthesis, crystal conformation, and activity of For-Hse(Me)-Leu-Phe-OMe.
The presence of the sulfur atom of the methionine side chain exerts significant effects at different levels on biochemical behavior of chemotactic N-formylpeptides. In order to acquire more information on this point, the synthesis, the conformation in the crystal, and the activity of For-Hse(Me)-Leu-Phe-OMe (2)--an oxygen analogue of For-Met-Leu-Phe-OMe (fMLP-OMe) containing the O-methyl-L-homoserine in place of the native methionine at position 1--is reported. The new analogue 2 adopts a conformation that is extended at the first two residues and folded at the C-terminal phenylalanine. This conformation is different from that of the parent fMLP-OMe and strikingly similar to that adopted by fMLP-OBu(t). The side-chain spatial orientation of 2 corresponds to that adopted by fMLP-OH when cocrystallized with an immunoglobulin possessing binding properties similar to those of neutrophil receptors. When tested on human neutrophils the formylpeptide 2 is more active than the parent in the stimulation of directed mobility and maintains both the granule enzyme release activity and the superoxide anion production.
Torrini
I
I
Dipartimento di Studi Farmaceutici, Università La Sapienza, Roma, Italy.
Pagani Zecchini
G
G
Paglialunga Paradisi
M
M
Lucente
G
G
Gavuzzo
E
E
Mazza
F
F
Pochetti
G
G
Traniello
S
S
Spisani
S
S
D000595:Amino Acid Sequence; D002630:Chemotactic Factors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003460:Crystallization; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation
D002630:Chemotactic Factors; D009842:Oligopeptides; C085962:formyl-methylhomoseryl-leucyl-phenylalanine methyl ester; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester