Biological variation responses in fMLP‐OMe analogs, introducing bulky protecting groups on the side‐chain of hydrophilic residues at position 2

Abstract

for-Met-Ser(Bzl)-Phe-OMe, for-Met-Cys(Bzl)-Phe-OMe, for-Met-Tyr(Bzl)-Phe-OMe and for-Met-Lys(Z)-Phe-OMe were synthesized to investigate the importance of a bulky protecting group on the side-chain of a hydrophilic residue at position 2 on the biological activities of human neutrophils. Our results indicate that these compounds do not trigger a good chemotactic response, which, in any case, is not improved with respect to that induced by the analogs with the unprotected residues. Instead, both superoxide anion production and, particularly, lysozyme release are more efficient.

Are formyl peptide receptors novel targets for therapeutic intervention in ischaemia–reperfusion injury?

“…To characterise further FPR interactions in phagocytes and subsequent cellular activation, several fMLP-OMe analogues have been synthesized [26] including for-Met-Leu-Cys(OMe)-Cys-Leu-Met-fpr, which binds to FPR1 [27]. Recently, fMLP-OMe analogues with receptor affinity greater than that of the parent fMLP-OMe have been synthesized, creating the potential for use as carriers for drugs [11].…”

Conformational investigations on analogs of inflammation response inducing chemotactic tripeptide fMLP

“…The retroisomer of fMLP, i.e., CHO–Phe–Leu–Met–NH 2 and its D analogs were found to be 100 to 10,000 times less active 74. Many other formyl peptides were also examined recently, for biological activities;75–95…”

“…To probe the structural requirement, these groups were mutated with residues having different steric, charge, and hydrophobic groups, and constraints were introduced to achieve the desired conformation. A large number of analogs of fMLP have been designed and synthesized, examined for their biological activities, and quite a few have also been studied for their conformation using X‐ray crystallography and NMR techniques 2, 9–22, 52–95. Results of conformational and activity studies on these peptides are summarized in Table V.…”