Computational study of the electronic structure characterization of a novelanti-inflammatory tripeptide derived from monocyte locomotion inhibitoryfactor (MLIF)-pentapeptide

The influence of electron donor and electron acceptor groups on the electronic structure of the anti‐inflammatory tripeptide Cys‐Asn‐Ser

“…In contrast, the electron donor groups provoke a decrement in the relative acidity of the H2. [12]; so that it seems that one of the features of the observed stability for the CNS tripeptide might be associated with a short hydrogen bond distance. In Table I, we have also reported values for the PAs (DE PA ) obtained from isodesmic reactions.…”

“…In Table I, we tabulate the values of the deprotonation energies (DE) of the CNS and theirs derivative peptides. We selected H2 hydrogen atoms to study the CNS tripeptide's relative acidity it was previously shown [12] that this hydrogen atom is involved in these peptide's chemical reactivity and geometric stability (see Fig. 1).…”

“…Thus, in Table II, we present the values of some selected bond orders: N1AH2, N15AH19, C22AO25, C23AO28, S37AH39, O12AH18, O14AH24, and C22AR. We first analyze the tripeptide's Cys (S37AH39), Asn (N15AH19), and Ser (N1AH2), (O12AH18), and (O14AH24) bond orders, respectively, as a smaller bond order should be indicative of a more acidic group [12,21,22]. We are able to observe that bond order for Ser (N1AH2) and (O14AH24) possess the smallest value with respect to Asn (N15AH19), Cys (S37AH39), and Ser (O12AH18) of CNS and its peptide derivatives, respectively.…”

“…At the same time, Morales-Martínez et al [11] carried out experimental studies in in vivo and in vitro models on the novel CNS tripeptide's anti-inflammatory activity with >95% purity and synthesized by the American Peptide Company; they found that the CNS tripeptide's maintained 100% of its biological and anti-inflammatory properties, similar to the MLIF; thus, experimentally verifying the pharmacophore group's anti-inflammatory activity proposed in the MLIF molecule predicted theoretically [10]. Recently, Barrientos-Salcedo et al [12] carried out calculations using second-order Møl-ler-Plesset perturbation theory (MP2) and density functional theory (DFT) theoretical levels to characterize with detail the electronic structure, physicochemical properties, and geometric parameters utilizing standard and complementary density descriptors of the CNS tripeptide. They found that N1AH2 bond possesses smallest deprotonation energy values with respect to S37AH39 bond.…”

“…Also they analyzed different quantum chemical descriptors, and they found important interaction sites, particularly on H2 and H39 atoms, suggesting that these atoms could be exposed to nucleophilic attacks. Additionally, results revealed that the CNS tripeptide could form hydrogen bonds between COHNH2ÁÁÁÁO25C, suggesting that the presence of the hydrogen bond might contribute to an increase in the CNS tripeptide's structural stability [12]. Hence, the aim of this study consists on carrying out a study at the B3LYP/6-311þG(2d,2p)/6-311þG(d,p) level of theory of 10 tripetides derivatives from CNS to analyze the effect that provokes the electron donor and electron withdrawing substituent's groups in the side chain of the asparagine amino acid, on the electronic and physicochemical properties of CNS and its derivatives, so as to improve the antiinflammatory activity of these novel tripeptides.…”