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Full Length
Research Paper
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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
Babak Khalili Hadad1*, Hadis Soltani2,
Sara Nouroozi3 and Fatemeh Navaie1
1Department
of Biological Sciences, Faculty of Sciences, Islamic Azad
University, Roudehen Branch, Roudehen, Iran.
2Young
Researcher Clubs, Roudehen Branch, Islamic Azad University,
Roudehen, Iran.
3Department
of Biological Sciences, Faculty of Sciences, Islamic Azad
University, Pishva Branch, Varamin, Iran.
*Corresponding author. E-mail:
khalili@riau.ac.ir.
Tel: +98 9123177387. Fax: +98 21 77295628.
Accepted 8 December, 2011 |
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Abstract |
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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.
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