N-terminal α-amino group modification of antibodies using a site-selective click chemistry method.
MAbs
; 10(5): 712-719, 2018 07.
Article
en En
| MEDLINE
| ID: mdl-29652547
ABSTRACT
Site-specific conjugation of small molecules to antibody molecules is a promising strategy for generation of antibody-drug conjugates. In this report, we describe the successful synthesis of a novel bifunctional molecule, 6-(azidomethyl)-2-pyridinecarboxyaldehyde (6-AM-2-PCA), which was used for conjugation of small molecules to peptides and antibodies. We demonstrated that 6-AM-2-PCA selectively reacted with N-terminal amino groups of peptides and antibodies. In addition, the azide group of 6-AM-2-PCA enabled copper-free click chemistry coupling with dibenzocyclooctyne-containing reagents. Bifunctional 6-AM-2-PCA mediated site-specific conjugation without requiring genetic engineering of peptides or antibodies. A key advantage of 6-AM-2-PCA as a conjugation reagent is its ability to modify proteins in a single step under physiological conditions that are sufficiently moderate to retain protein function. Therefore, this new click chemistry-based method could be a useful complement to other conjugation methods.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Inmunoconjugados
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Bibliotecas de Moléculas Pequeñas
/
Química Clic
/
Anticuerpos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
MAbs
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2018
Tipo del documento:
Article