Modulation of co‐stimulatory signal from CD2–CD58 proteins by a grafted peptide
| Autor: | Pravin Parajuli, Achyut Dahal, Rushikesh Sable, Leeza Shrestha, Seetharama D. Jois, Veena Taneja, Ted J. Gauthier |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
T-Lymphocytes
Trypsin inhibitor CD2 Antigens Peptide Binding Competitive Peptides Cyclic 01 natural sciences Biochemistry Article Cell Line Protein–protein interaction Drug Discovery Cell Adhesion Humans Amino Acid Sequence Protein Interaction Maps Surface plasmon resonance Cell adhesion Pharmacology Alanine chemistry.chemical_classification Binding Sites Protein Stability 010405 organic chemistry Chemistry Organic Chemistry Alanine scanning CD58 Antigens 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Enzyme Drug Design Biophysics Molecular Medicine Trypsin Inhibitors Protein Binding |
| Zdroj: | Chem Biol Drug Des |
| ISSN: | 1747-0285 1747-0277 |
| DOI: | 10.1111/cbdd.13797 |
| Popis: | Peptides were designed to inhibit the protein-protein interaction of CD2 and CD58 to modulate the immune response. This work involved the design and synthesis of eight different peptides by replacing each amino acid residue in peptide 6 with alanine as well as grafting the peptide to the sunflower trypsin-inhibitor framework. From the alanine scanning studies, mutation at position 2 of the peptide was shown to result in increased potency to inhibit cell adhesion interactions. The most potent peptide from the alanine scanning was further studied for its detailed three-dimensional structure and binding to CD58 protein using surface plasmon resonance and flow cytometry. This peptide was used to graft to the sunflower trypsin inhibitor to improve the stability of the peptide. The grafted peptide, SFTI-a1, was further studied for its potency as well as its thermal, chemical, and enzymatic stability. The grafted peptide exhibited improved activity compared to our previously grafted peptide and was stable against thermal and enzymatic degradation. |
| Databáze: | OpenAIRE |
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