Electronic properties study of reaction mechanism of C-N bonding formation in Ac-DT-NH2 and Ac-TD-NH2 peptide by ab initio computational on HF/6-31g** level

Abstract

Abstract The peptide has many functions, which one of the function is delivering the drug to overcome some diseases in the brain. However, drug delivery to the brain is hindered by the paracellular pathway of Blood Brain Barrier (BBB). This pathway has a tight junction or a tight intersection which is the result of naturally intercellular cadherin-cell interactions. One approach to increase delivering of drug to the brain is by increasing the porosity of the paracellular pathway of tight junction which was already done by modulating the intercellular cadherin-cell interactions using the synthesized ADTC-1 (Ac-ADTPPVC-NH2) peptide which derived from natural cadherin. One the sequence of two amino acids in ADTC-1 peptide is Ac-DT-NH2 between aspartate (D) and threonine (T) amino acids which is similar within natural cadherin and is not Ac-TD-NH2. So that, the purpose of this reseach is to prove and determine the most preferred reaction mechanism between Ac-DT-NH2 and Ac-TD-NH2 peptide which occurred in natural cadherin. In this study, the computational approach on the level of theory and basis set HF/SCF 6-31g ** was used to calculate the electronic properties of all molecules involved in Ac-DT-NH2 and Ac-TD-NH2 peptide synthesis to prove and determine the most preferred reaction mechanism. The results show that the I reaction mechanism which produced Ac-DT-NH2 peptide formed with the activation energy Ea was 1329.23 kJmol−1. While the IV reaction mechanism which produced Ac-TD-NH2 peptide had Ea 2470.19 kJmol−1. The study concluded that the I reaction mechanism produced Ac-DT-NH2 which is similar within natural cadherin synthesis was proved more easily and preferred than the IV reaction mechanism. Both the I and IV reaction mechanisms were exothermic with ΔH reaction enthalpy -6.075 kJmol−1 and -6.092 kJmol−1 respectively.