Synthesis, conformation and biological activity of centrally modified pseudopeptidic analogues of For-Met-Leu-Phe-OMe.
For-Met-betaAlapsi[CSNH]-Phe-OMe (3), For-Met-betaAlapsi[CH2NH]-Phe-OMe (5), For-Met-NH-pC6H4-SO(2-Phe-OMe 8a), For-Met-NH-mCH4-SO2-Phe-OMe (8b) and the corresponding N-Boc precursors (2, 4, 7a, b) have been synthesized and their activity towards human neutrophils has been evaluated in comparison with that shown by the reference tripeptide For-Met-Leu-Phe-OMe (fMLF-OMe). Chemotaxis, lysozyme release and superoxide anion production have been measured. (1)H NMR titration experiments and IR spectra have been discussed in order to ascertain the preferred solution conformation adopted by the tripeptide 3 with particular reference to the presence of a folded conformation centred at the centrally positioned thionated beta-residue.
Giordano
C
C
Sezione di Roma, Dipartimento di Studi Farmaceutici, Istituto di Chimica Biomolecolare del CNR, Università degli Studi di Roma La Sapienza, Rome, Italy.
Lucente
G
G
Masi
A
A
Paglialunga Paradisi
M
M
Sansone
A
A
Spisani
S
S
D002634:Chemotaxis, Leukocyte; D006801:Humans; D015394:Molecular Structure; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D012997:Solvents; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism
D010455:Peptides; D012997:Solvents; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester