SnoopLigase Enables Highly Efficient Generation of C-C-Linked Bispecific Nanobodies Targeting TNF-α and IL-17A.
Bioconjug Chem
; 33(8): 1446-1455, 2022 08 17.
Article
em En
| MEDLINE
| ID: mdl-35938675
ABSTRACT
Bispecific antibodies (bis-Nbs) have been extensively developed since the concept was devised over the decades. Taking advantage of the superior characteristics of nanobodies, bis-Nbs exhibit an emerging tendency to become the new generation of research and diagnostic tools. Traditional strategies to connect the homo- or heterogeneous monomers are commonly applied, but there are still technical issues to generate the bispecific molecules as efficiently as designed. Here, we utilize SnoopLigase to directly tether the C terminus (C-C) of the tagged nanobodies against tumor necrosis factor-α (TNF-α) and interleukin-17A (IL-17A). Under optimal conditions, the yield of C-C-linked bis-Nbs can reach as high as 70% due to the existence of SnoopLigase. The prepared bis-Nbs possessed similar or even higher affinity as the monomers and significantly inhibited the proliferation and migration of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) induced by TNF-α and IL-17A. This study provides an innovative route for using SnoopLigase to realize a highly efficient generation of C-C-linked bis-Nbs. The approach can be applied to different and multicomponent systems for their potential applications in disease diagnosis and treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
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Anticorpos Biespecíficos
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Anticorpos de Domínio Único
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Sinoviócitos
Limite:
Humans
Idioma:
En
Revista:
Bioconjug Chem
Ano de publicação:
2022
Tipo de documento:
Article