Keywords: Actriib Receptor, Binding, Docking, Peptides, Bone Morphogenetic Protein, Article, Binding Affinity, Controlled Study, Enzyme Linked Immunosorbent Assay, Human, Human Cell, Nuclear Magnetic Resonance Spectroscopy, Priority Journal, Protein Conformation, Protein Structure, Receptor Binding, Surface Plasmon Resonance,
Affiliations: *** IBB - CNR ***
Department of Pharmacy, University of Naples federico II, via Mezzocannone 16, Naples, Italy
Institute of Biostructure and Bioimaging (IBB), CNR, via Mezzocannone, 16, Naples, Italy
CIRPeB, University of Naples federico II, via Mezzocannone 16, Naples, Italy
Department of Molecular Medicine, University of Padua, via Gabelli 63, Padua, Italy
Department of Industrial Engineering, University of Padua, via Marzolo 9, Padua, Italy
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Osteogenic properties of a short BMP-2 chimera peptide
Bone morphogenetic proteins (BMPs) play a key role in bone and cartilage formation. For these properties, BMPs are employed in the field of tissue engineering to induce bone regeneration in damaged tissues. To overcome drawbacks due to the use of entire proteins, synthetic peptides derived from their parent BMPs have come out as promising molecules for biomaterial design. On the structural ground of the experimental BMP-2 receptor complexes reported in the literature, we designed three peptides, reproducing the BMP-2 region responsible for the binding to the type II receptor, ActRIIB. These peptides were characterized by NMR, and the structural features of the peptide-receptor binding interface were highlighted by docking experiments. Peptide-receptor binding affinities were analyzed by means of ELISA and surface plasmon resonance techniques. Furthermore, cellular assays were performed to assess their osteoinductive properties. A chimera peptide, obtained by combining the sequence portions 73-92 and 30-34 of BMP-2, shows the best affinity for ActRIIB in the series and represents a good starting point for the design of new compounds able to reproduce osteogenic properties of the parent BMP-2.
Osteogenic properties of a short BMP-2 chimera peptide
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