Cyclo[(-D-Gly3-L-Asp3)] in combination with C and D polypeptide chains of NS3; suggestion a novel nanoparticle to stimulate immune system against hepatitis C

Abstract

Development of a hepatitis C vaccine is a challenge. Although several vaccines are currently under development, no effective vaccine is currently available. Non structural protein- NS3- can stimulate TH1 and make enhancement in NS3-specific interferon-γ (IFN-γ) serum level. It is thought to use nanoparticles which are biodegradable and safe to body can be a novel approach to deliver epitops as vaccine. Adding the polypeptides components of NS3 on cyclic hexa peptide nanorings with the ability to stimulate immune system without any risk of infection is the main goal of this research. In present study, the nano structures were designed using HyperchemTM 8.0.6 software and ArgusLab 4.0.1 package. Cyclo [(-D-G3-L-D3)] nanoring has been studied by quantum mechanical calculations within the Onsager self- consistent reaction field model at room and critical body temperatures, using Gaussian 03 package. Radius of gyration and φ and ψ rotation were analyzed with VMD 1.8.2. Montecarlo molecular mechanic method in both MM+ and Bio+ (Charmm) force fields were operated in 200pSec. 1, 2 and 3 polypeptide chains of C and D, separated from NS3 of protease (PDB ID: 1NS3), were substituted to the core. It was revealed that by increasing the polypeptide substituent, the potential energy was increased in systems. The mean of relative potential in Cyclo [(-D-G3-L-D3)] substituted with D-polypeptide chain was about two times more stable than the one of C- polypeptide chain, in the same condition. Φ and ψ, changes due to temperature arising were approved in these cases. Although both C and D polypeptide chains were stable in water medium (such as body condition), the results revealed that D chain is more stable to use for nanovaccine fabrication. The Cyclo [(-D-G3-L-D3)] with three substituent of D-chain is suggested, based on results. Key words: Cyclo[(-D-Gly3-L-Asp3)], non structural protein- NS3, vaccine, hepatitis C, Ramachandran plot.