Design and Synthesis of Monobody Variants with Low Immunogenicity.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
09 Nov 2023
09 Nov 2023
Historique:
received:
04
08
2023
accepted:
27
09
2023
pmc-release:
09
11
2024
medline:
17
11
2023
pubmed:
17
11
2023
entrez:
17
11
2023
Statut:
epublish
Résumé
Mirror-image proteins (d-proteins) are promising scaffolds for drug discovery because of their high proteolytic stability and low immunogenic properties. Facile and reproducible processes for the preparation of functional d-proteins are required for their application in therapeutic biologics. In this study, we designed and synthesized a novel monobody variant with two cysteine substitutions that facilitate the synthetic process via sequential native chemical ligations and improve protein stability by disulfide bond formation. The synthetic anti-GFP monobody in this model study exhibited good binding affinity to the target enhanced green fluorescent protein. In vivo administration of the synthetic anti-GFP monobody (l-monobody) to mice induced antidrug antibody (ADA) production, whereas no ADA production was observed following immunization with the mirror-image anti-GFP monobody (d-monobody). These results suggest that the synthetic d-monobody is a non-antibody protein scaffold with low immunogenic properties.
Identifiants
pubmed: 37974939
doi: 10.1021/acsmedchemlett.3c00342
pmc: PMC10641909
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1596-1601Informations de copyright
© 2023 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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