Self-assembled antibody multimers through peptide nucleic acid conjugation.
J Am Chem Soc
; 135(1): 340-6, 2013 Jan 09.
Article
em En
| MEDLINE
| ID: mdl-23210862
ABSTRACT
With the recent clinical success of bispecific antibodies, a strategy to rapidly synthesize and evaluate bispecific or higher order multispecific molecules could facilitate the discovery of new therapeutic agents. Here, we show that unnatural amino acids (UAAs) with orthogonal chemical reactivity can be used to generate site-specific antibody-oligonucleotide conjugates. These constructs can then be self-assembled into multimeric complexes with defined composition, valency, and geometry. With this approach, we generated potent bispecific antibodies that recruit cytotoxic T lymphocytes to Her2 and CD20 positive cancer cells, as well as multimeric antibody fragments with enhanced activity. This strategy should accelerate the synthesis and in vitro characterization of antibody constructs with unique specificities and molecular architectures.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos Fab das Imunoglobulinas
/
Ácidos Nucleicos Peptídicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos