New fMLF-OMe analogues containing constrained mimics of phenylalanine residue.
In the context of a research program aimed at elucidating the HCO-Met-Leu-Phe-OMe (fMLF-OMe) structural features which control interactions with the receptor in correspondence with the C-terminal residue, four different analogues of the native ligand have been synthesized and evaluated. Compounds 1-3 possess the general formula HCO-Met-Leu-Xaa-OMe with Xaa = N-benzylglycine, N-benzylphenylalanine, and alpha,alpha-dibenzylglycine, respectively. In the analogue 4 the constraint at the C-terminus has been obtained by incorporating a 2-oxopiperazine ring, made up of two phenylalanine residues, to replace the native C-terminal Phe residue. The consequences of the chemical modifications on the activity of the new analogues are discussed.
Torrini
I
I
Dipartimento di Studi Farmaceutici, Università La Sapienza, Roma, Italy.
Mastropietro
G
G
Pagani Zecchini
G
G
Paglialunga Paradisi
M
M
Lucente
G
G
Spisani
S
S
D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018716:Molecular Mimicry; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010649:Phenylalanine / Q000737:chemistry / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D010649:Phenylalanine; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester