Background:
Peptibodies, the hybrid of peptides and antibodies, represent a novel
strategy in therapeutic use. Previously, we computationally designed an antiangiogenic peptibody
PbHRH, which fused the HRH peptide with angiogenesis-suppressing effect and human IgG1 Fc
fragment using Romiplostim as template. Molecular modeling and simulation results indicated that
it would be a potential drug for the treatment of those angiogenesis related pathological disorders.
However, its immunogenicity is not known.
Methods:
Several bioinformatics tools are used to predict the potential epitopes for the evaluation
of the immunogenicity of PbHRH. Romiplostim is set as the control. IEDB-recommended method
is used in MHC-I and MHC-II binding prediction, and the IEDB web server
(http://tools.iedb.org/immunogenicity/) is used to determine the MHC-I immunogenicity of each
peptide.
Results:
In this work, some peptides are predicted to have the potential ability to bind to MHC-I
and MHC-II molecules both in PbHRH and Romiplostim as the potential epitopes. Most of these
selected peptides are exactly the same. Allele frequency analysis shows a low population
distribution. Combined with the analysis of MHC-I immunogenicity prediction, both HRH and
PbHRH show low immunogenicity.
Conclusion:
Some potential epitopes which could bind to both MHC-I and MHC-II molecules
are predicted using bioinformatics tools. The comparative analysis with Romiplostim and the
results of MHC-I immunogenicity prediction indicate the low immunogenicity of both HRH and
PbHRH. Thus, we form a strategy to evaluate the immunogenicity of peptibodies for the future
improvement.
Computational Design of Antiangiogenic Peptibody by Fusing Human IgG1 Fc Fragment and HRH Peptide: Structural Modeling, Energetic Analysis, and Dynamics Simulation of Its Binding Potency to VEGF Receptor