Identification of Peptide Mimotope Ligands for Natalizumab

Abstract 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...

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Autores principales:	Laura E. Ruff, Jessica A. Pfeilsticker, Nicholas E. Johnsen, Sarah Nocchi, Bradley T. Messmer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Peptide Mimotopes Capture Reagent Phage Display Library Antigen Binding Site Peptide ELISA Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dbcb2a18d1b547218b99e669ed8adfff
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spelling	oai:doaj.org-article:dbcb2a18d1b547218b99e669ed8adfff2021-12-02T15:08:17ZIdentification of Peptide Mimotope Ligands for Natalizumab10.1038/s41598-018-32832-12045-2322https://doaj.org/article/dbcb2a18d1b547218b99e669ed8adfff2018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32832-1https://doaj.org/toc/2045-2322Abstract 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.Laura E. RuffJessica A. PfeilstickerNicholas E. JohnsenSarah NocchiBradley T. MessmerNature PortfolioarticlePeptide MimotopesCapture ReagentPhage Display LibraryAntigen Binding SitePeptide ELISAMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Peptide Mimotopes Capture Reagent Phage Display Library Antigen Binding Site Peptide ELISA Medicine R Science Q
spellingShingle	Peptide Mimotopes Capture Reagent Phage Display Library Antigen Binding Site Peptide ELISA Medicine R Science Q Laura E. Ruff Jessica A. Pfeilsticker Nicholas E. Johnsen Sarah Nocchi Bradley T. Messmer Identification of Peptide Mimotope Ligands for Natalizumab
description	Abstract 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.
format	article
author	Laura E. Ruff Jessica A. Pfeilsticker Nicholas E. Johnsen Sarah Nocchi Bradley T. Messmer
author_facet	Laura E. Ruff Jessica A. Pfeilsticker Nicholas E. Johnsen Sarah Nocchi Bradley T. Messmer
author_sort	Laura E. Ruff
title	Identification of Peptide Mimotope Ligands for Natalizumab
title_short	Identification of Peptide Mimotope Ligands for Natalizumab
title_full	Identification of Peptide Mimotope Ligands for Natalizumab
title_fullStr	Identification of Peptide Mimotope Ligands for Natalizumab
title_full_unstemmed	Identification of Peptide Mimotope Ligands for Natalizumab
title_sort	identification of peptide mimotope ligands for natalizumab
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/dbcb2a18d1b547218b99e669ed8adfff
work_keys_str_mv	AT lauraeruff identificationofpeptidemimotopeligandsfornatalizumab AT jessicaapfeilsticker identificationofpeptidemimotopeligandsfornatalizumab AT nicholasejohnsen identificationofpeptidemimotopeligandsfornatalizumab AT sarahnocchi identificationofpeptidemimotopeligandsfornatalizumab AT bradleytmessmer identificationofpeptidemimotopeligandsfornatalizumab
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Identification of Peptide Mimotope Ligands for Natalizumab

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