Recently, interest in small peptide molecules as potential drug candidates has revived. In this review, two series
of synthetic peptides and their selective effects on the inflammatory response have been described, focusing on the
intracellular pathways involved and on their therapeutic potential. A series of FDLFDLF analogs has been synthesized,
including either N- t-Boc or different N-ureido substituents. The free acid derivatives as they are good candidates as antiinflammatory
drugs are able to antagonize the multiple neutrophil functions evoked by N-formyl-L-methionyl-L-leucyl-Lphenylalanine
(fMLF), i.e. chemotaxis, superoxide anion production and lysozyme release. Their methyl-ester derivatives
are ineffective. The second series of peptides derives from the endogenous protein kinase C (PKC) inhibitor PKI55, a
55-amino acid protein, whose synthesis is induced by PKC activation, so that a feedback loop of inhibition is established.
In vitro experiments showed that PKI55 inhibits recombinant PKC isoforms α, β1, β2, γ, δ, ζ, ε; to identify the minimal
amino acid sequence of PKI55 protein maintaining the inhibitory effects on PKC, peptides derived from both C- and
N-terminal sequences have been synthesized. The N-terminal peptides 5 (MLYKLHDVCRQLWFSC), 8 (CRQLWFSC)
and 9 (CRQLW), that in human neutrophils retain the inhibitory activity on PKC, decrease the chemotaxis, and, in mice,
display anti-inflammatory and analgesic action, after both central and peripheral administration of very low doses.
Furthermore, the peptide 5 shows neuroprotective activity in a model of cerebral ischemia in vitro, favouring the recovery
of synaptic function. These findings suggest interesting possible therapeutic applications for these peptides.