Identification of Peptide Mimotope Ligands for Natalizumab
| Autor: | Bradley Todd Messmer, Sarah Nocchi, Laura E. Ruff, Jessica A. Pfeilsticker, Nicholas E. Johnsen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Phage display medicine.drug_class Science Integrin alpha4 Amino Acid Motifs Peptide Monoclonal antibody Phage Display Library Affinity maturation 03 medical and health sciences Epitopes 0302 clinical medicine Natalizumab Peptide Library medicine Capture Reagent Humans Peptide library Peptide Mimotopes chemistry.chemical_classification Multidisciplinary medicine.diagnostic_test Chemistry Mimotope Antigen Binding Site 030104 developmental biology Biochemistry Immunoassay Medicine Peptide ELISA 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-8 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Mimotope peptides selected from combinatorial peptide libraries can be used as capture reagents for immunoassay detection of therapeutic monoclonal antibodies (mAbs). We report the use of phage display libraries to identify peptide ligands (VeritopesTM) that bind natalizumab, a therapeutic mAb indicated for use in multiple sclerosis. PKNPSKF is identified as a novel natalizumab-binding motif, and peptides containing this motif demonstrated utility as capture reagents in enzyme-linked immunosorbent assays (ELISAs). A peptide containing the identified motif was shown to be competitive with the natural ligand (α4-integrin) and a neutralizing anti-idiotype antibody for natalizumab binding, indicating that VeritopesTM act as surrogate ligands that bind the antigen binding site of natalizumab. Affinity maturation further confirmed the motif sequence and yielded peptides with greater apparent affinity by ELISA. VeritopesTM are promising assay reagents for therapeutic drug level monitoring. |
| Databáze: | OpenAIRE |
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