DNA Framework Programmed Conformational Reconstruction of Antibody Complementary Determining Region.
Journal
JACS Au
ISSN: 2691-3704
Titre abrégé: JACS Au
Pays: United States
ID NLM: 101775714
Informations de publication
Date de publication:
23 Oct 2023
23 Oct 2023
Historique:
received:
22
08
2023
revised:
18
09
2023
accepted:
18
09
2023
medline:
27
10
2023
pubmed:
27
10
2023
entrez:
27
10
2023
Statut:
epublish
Résumé
The conformation of complementary determining region (CDR) is crucial in dictating its specificity and affinity for binding with an antigen, making it a focal point in artificial antibody engineering. Although desirable, programmable scaffolds that can regulate the conformation of individual CDRs with nanometer precision are still lacking. Here, we devise a strategy to program the CDR conformation by anchoring both ends of a free CDR loop to specific sites of a DNA framework structure. This method allows us to define the span of a single CDR loop with an ∼2 nm resolution. Using this approach, we create a series of DNA framework based artificial antibodies (DNFbodies) with varied CDR loop spans, leading to different antibody-antigen binding affinities. We find that an optimized single CDR loop (∼2.3 nm span) exhibits ∼3-fold improved affinity relative to natural antibodies, confirming the critical role of the CDR conformation. This study may inspire the rational design of artificial antibodies.
Identifiants
pubmed: 37885585
doi: 10.1021/jacsau.3c00492
pmc: PMC10598557
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2709-2714Informations de copyright
© 2023 The Authors. Published by American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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