Molecular characteristics of the tripeptide feG accounting for different biological activities

The tripeptide FEG (Phe-Glu-Gly) and its D-isomer feG are potent anti-inflammatory peptides that reduce type I immediate hypersensitivity reactions (antigen-induced contraction of sensitized intestine), and inhibit the binding of CD16b (FCyRIII) antibody to human neutrophils. However, significant differences exist in the structure activity relationships (SAR) with FEG-like peptides for these two activities. By comparing biological activities to the topological features of FEG and its analogues this study identifies the distinguishing features of the peptides that explain the differential SAR on the immediate hypersensitivity reaction and CD16b antibody binding. Using DeepView (http://www.expasy.org/spdbv/), the distances between side-chain atoms and the angles between side-chain terminal carbon residues and their backbone juncture were determined. The electrostatic force field of the peptides was calculated using DeepView, which employs the GROMOS96 43B1 parameter set. The primary topological feature of FEG-like molecules that impacts the immediate hypersensitivity reaction was the relative positioning of the aromatic ring to the carboxyl group of position-2 amino acid. In contrast, the electrostatic potential of the peptides primarily determined the inhibition of CD16b antibody binding, although the separation of the carboxyl groups on position-2 amino acid and the C-terminal provided a topological component to biological activity. Thus, the topological features and the electrostatic potential of FEG and its analogues account for differential SAR, and suggest that the FEG may act on several distinct recognition sites.