Computational study of the electronic structure characterization of a novel anti-inflammatory tripeptide derived from monocyte locomotion inhibitory factor (MLIF)-pentapeptide

• Published in: European journal of medicinal chemistry Vol. 44; no. 8; pp. 3114 - 3119
• Main Authors: BARRIENTOS-SALCEDO, Carolina, RICO-ROSILLO, Guadalupe, GIMENEZ-SCHERER, Juan Antonio, SORIANO-CORREA, Catalina
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier 01.08.2009
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Computer Simulation; Drug Design; Electrons; Humans; Medical sciences; Models, Molecular; Oligopeptides - chemistry; Oligopeptides - pharmacology; Pharmacology. Drug treatments; Protein Conformation; Quantum Theory; Static Electricity; Protozoa; Lobosea; Computer simulation; Ab initio method; Antiinflammatory agent; Tripeptide; Theoretical study; Entamoeba histolytica; Acidity; Small peptides Acidity Electronic structure Ab initio Density functional theory; Electronic structure; Anti-inflammatory peptide; Sulfur peptide; Density functional method; Chemical properties; Moller Plesset partition; Pentapeptide
• DOI: 10.1016/j.ejmech.2009.03.003
• ISSN: 0223-5234

The structure and properties of molecules are determined by their charge-density distribution. Several works have shown that electron delocalization along the peptide backbone and side-chain modulates the physical and chemical features of peptides and protein properties. Research on Entamoeba histolytica-soluble factors led to the identification of the pentapeptide Met-Gln-Cys-Asn-Ser, with anti-inflammatory in vivo and in vitro effects. A synthetic pentapeptide, Met-Pro-Cys-Asn-Ser, maintained the same anti-inflammatory actions in experimental assays. A previous theoretical study allowed proposing the Cys-Asn-Ser tripeptide (CNS tripeptide) as the pharmacophore group of both molecules. This theoretical hypothesis was recently confirmed experimentally. The aim of this study was to characterize the electronic structure and physico-chemical properties of the CNS tripeptide through a theoretical study at the second-order Møller-Plesset perturbation theory (MP2) and density functional theory (DFT) theoretical levels. Our results in deprotonation energies show that the hydrogen atom (H2) of the serine-amide group possesses acidic characteristics. This result was confirmed by means of a study of bond order. Atomic charges, dipole moment, frontier molecular orbitals (Highest occupied molecular orbital [HOMO-1] and Lowest unoccupied molecular orbital [LUMO+1]), and electrostatic potential isosurface and its geometric parameters permitted to characterize its electronic structure and physico-chemical features and to identify some reactive sites that could be associated with this tripeptide's anti-inflammatory activity.