Electronic structure and physicochemical properties of the anti-inflammatory pentapeptide produced by Entamoeba histolytica: A theoretical study

The selective anti-inflammatory effects of the pentapeptide [Met-Gln-Cys-Asn-Ser] with anti-inflammatory properties are manifest in both in vitro and in vivo models. A synthetic structure considered by our group displays the same effects; nonetheless, this is not so for a scrambled version using the same amino acids in a different sequence [Gln-Cys-Met-Ser-Asn]. When the amino acid proline substituted glutamine as the second residue [i.e. Met-Pro-Cys-Asn-Ser], the anti-inflammatory effects of monocyte locomotion inhibitory factor (MLIF) were preserved, although with a weaker effect observed on the respiratory burst and enhanced inhibition of delayed hypersensitivity. The above motivates us to study the electronic structure and the physicochemical properties of these three peptides through a theoretical study at the Hartree-Fock and DFT (B3LYP) levels, with the aim of understanding this behavior from an electronic structure framework. Geometric analysis allowed us to identify a pharmacophore group at the acidic end of the molecule [i.e. …Cys-Asn-Ser]. The electrostatic charge of the pharmacophore group and the charge of the sulphur atom (SCys37) in the cysteine group are affected by the presence of electron-attracting groups. These results are further supported by a bond order study and an atomic charges analysis. The structural and physicochemical features studied here could be associated with the anti-inflammatory activity of these peptides.