The Cys-Asn-Ser carboxyl-terminal end group is the pharmacophore of the amebic anti-inflammatory monocyte locomotion inhibitory factor (MLIF)

Abstract

The monocyte locomotion inhibitory factor (MLIF) is an anti-inflammatory oligopeptide produced by Entamoeba histolytica. Among its different effects, it inhibits locomotion of human monocytes, hence its original name. Previous experimental studies have shown that the anti-inflammatory properties of MLIF (Met-Gln-Cys-Asn-Ser) remained when aminoacid glutamine was substituted by a proline in the second position (pMLIF: Met-Pro-Cys-Asn-Ser). By changing the order of MLIF amino acids, the resulting scrambled oligopeptide (sMLIF: Gln-Cys-Met-Ser-Asn) has failed activity. By means of ab initio study at the Hartree–Fock and Density Functional Theory levels, it was found that MLIF and pMLIF peptides maintain a great structural similarity among the last three amino acids (…Cys-Asn-Ser) predicting a pharmacophore. The objective of this work was to experimentally verify in vivo and in vitro the existence of the pharmacophore group in MLIF. We assayed three tripeptides by respiratory burst and delayed hypersensitivity skin reactions. The tripeptide Cys-Asn-Ser carboxyl-terminal end group maintained 100% of its biological properties, as well as the anti-inflammatory activity of MLIF, while the other tripeptides tested did not do that.