Design of Beta-sheet Hairpin Peptide Targeting to B7H6 Protein
Poster Number
12a
Introduction/Abstract
B7-H6 is one of B7 family member protein recently found as a potential cancer therapy target. It functionally activates natural killer (NK) cells and increases their cytolysis and secretion of interferon-γ. Research results showed that B7-H6 only highly expressed on tumor cells, such as melanomas, T and B lymphomas, neuroblastomas, and carcinomas. This makes it a very promising therapeutic target for cancer therapy. Anti-B7-H6 antibody has been developed for research use, but B7-H6 peptide ligand has not been reported. We select B7H6 as target and design new peptide ligand based on the crystal structure of B7H6 to its ligand NKp30 binding complex.
Purpose
Reveal a method to design targeting peptide with beta-sheet conformation based on the crystal structure of protein binding.
Method
According to the crystal structure of B7-H6/NKp30 complex, binding sites on B7-H6 protein surface are identified. The amino acids including Ile50, Gly51, Ser52, Val53, Glu111, Leu113 and Gly114 on the NKp30 protein is interacting with B7H6 protein. These amino acids come from two nearby sheet backbone and if we link them together, we will have a small beta-sheet hairpin peptide. Further we use the Trp-Trp and Cys-Cys interaction to stabilize the hairpin structure. In this way, we have our designed beta-sheet hairpin peptides. 4 peptides are designed based on the docking results. Peptides are synthesized using the standard fmoc solid phase synthesis. HPLC and mass spectrometry are used to characterize the products. Cellular uptake experiment is conducted to test the targeting effect.
Results
Docking results show that the peptides have the potential to bind to the area as we designed. The mass peak of synthesized products ion are found from the mass spectra. The purity of peptide products are determined by HPLC. The cellular uptake results indicate that #1 and #4 peptides has more uptake by the cells compared to the other peptide and the negative cells group.
Significance
Peptide ligand plays an important role in drug targeting delivery. It has many advantages of simple structure and easy synthesis method. Up to now, discovery of peptide ligand mainly relies on phage display, which costs huge money and time. In this research, we want to design the peptide ligand based on the analysis of the protein binding structure.
Location
DeRosa University Center
Format
Poster Presentation
Poster Session
Morning 10am-12pm
Design of Beta-sheet Hairpin Peptide Targeting to B7H6 Protein
DeRosa University Center
B7-H6 is one of B7 family member protein recently found as a potential cancer therapy target. It functionally activates natural killer (NK) cells and increases their cytolysis and secretion of interferon-γ. Research results showed that B7-H6 only highly expressed on tumor cells, such as melanomas, T and B lymphomas, neuroblastomas, and carcinomas. This makes it a very promising therapeutic target for cancer therapy. Anti-B7-H6 antibody has been developed for research use, but B7-H6 peptide ligand has not been reported. We select B7H6 as target and design new peptide ligand based on the crystal structure of B7H6 to its ligand NKp30 binding complex.
