Development of novel humanized VHH synthetic libraries based on physicochemical analyses.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 08 2024
22 08 2024
Historique:
received:
14
02
2024
accepted:
19
08
2024
medline:
23
8
2024
pubmed:
23
8
2024
entrez:
22
8
2024
Statut:
epublish
Résumé
Due to the high affinity and specificity of antibodies toward antigens, various antibody-based applications have been developed. Recently, variable antigen-binding domains of heavy-chain antibodies (VHH) have become an attractive alternative to conventional fragment antibodies due to their unique molecular characteristics. As an antibody-generating strategy, synthetic VHH libraries (including humanized VHH libraries) have been developed using distinct strategies to constrain the diversity of amino acid sequences. In this study, we designed and constructed several novel synthetic humanized VHH libraries based on biophysical analyses conducted using the complementarity determining region-grafting method and comprehensive sequence analyses of VHHs deposited in the protein data bank. We obtained VHHs from the libraries, and hit clones exhibited considerable thermal stability. We also found that VHHs from distinct libraries tended to have different epitopes. Based on our results, we propose a strategy for generating humanized VHHs with distinct epitopes toward various antigens by utilizing our library combinations.
Identifiants
pubmed: 39174623
doi: 10.1038/s41598-024-70513-4
pii: 10.1038/s41598-024-70513-4
doi:
Substances chimiques
Peptide Library
0
Complementarity Determining Regions
0
Epitopes
0
Immunoglobulin Heavy Chains
0
Antigens
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
19533Subventions
Organisme : Japan Society for the Promotion of Science
ID : 21H05090
Organisme : Japan Society for the Promotion of Science
ID : 19H05766
Organisme : Japan Society for the Promotion of Science
ID : 20H02531
Organisme : JST-Mirai Program
ID : MJMI21G6
Organisme : Japan Agency for Medical Research and Development
ID : 18ak0101100
Organisme : Japan Agency for Medical Research and Development
ID : 19am0401010
Organisme : Japan Agency for Medical Research and Development
ID : 20mk0101170
Organisme : JST-CREST Program
ID : MJCR20H8
Informations de copyright
© 2024. The Author(s).
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