title: For-Met-Lys-Phe-For-Met-Lys-Phe-: a new cyclic analogue of the chemotactic formylpeptides.
abstract: As a continuation of the studies on chemotactic N-formylpeptides, we report here the synthesis and activity of a new cyclic analogue of the prototypical ligand For-Met-Leu-Phe-OMe. The new compound For-Met-Lys-Phe-For-Met-Lys-Phe- (4) contains a 20-membered cyclic moiety made up of a dimeric -Lys-Phe- sequence in which For-Met is attached to each Lys alpha-NH2 and hence remains outside the ring. The conformation in the crystal of the cyclic precursor of 4, namely Boc-Lys-Phe-Boc-Lys-Phe- (2) and the activity of the structurally related linear analogue For-Met-Lys(Z)-Phe-OBzl (6), have also been examined. The new analogues 4 and 6 are active as chemoattractants, secretagogues, and superoxide anion generating agents, when tested on human neutrophils. The structure-activity relationship is discussed and related to that of a previously studied cyclic model.
authors.affiliation: Dipartimento di Studi Farmaceutici, Chimica del Farmaco del CNR Università La Sapienza, Roma, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Torrini
authors.forename: G P
authors.initials: GP
authors.lastname: Zecchini
authors.forename: M P
authors.initials: MP
authors.lastname: Paradisi
authors.forename: G
authors.initials: G
authors.lastname: Lucente
authors.forename: E
authors.initials: E
authors.lastname: Gavuzzo
authors.forename: F
authors.initials: F
authors.lastname: Mazza
authors.forename: G
authors.initials: G
authors.lastname: Pochetti
authors.forename: S
authors.initials: S
authors.lastname: Traniello
authors.forename: S
authors.initials: S
authors.lastname: Spisani
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D010456:Peptides, Cyclic; D009240:N-Formylmethionine Leucyl-Phenylalanine