For-Met-Lys-Phe-For-Met-Lys-Phe-: a new cyclic analogue of the chemotactic formylpeptides.
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.
Torrini
I
I
Dipartimento di Studi Farmaceutici, Chimica del Farmaco del CNR Università La Sapienza, Roma, Italy.
Zecchini
G P
GP
Paradisi
M P
MP
Lucente
G
G
Gavuzzo
E
E
Mazza
F
F
Pochetti
G
G
Traniello
S
S
Spisani
S
S
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
D010456:Peptides, Cyclic; D009240:N-Formylmethionine Leucyl-Phenylalanine