Improved ligand binding by antibody-aptamer pincers.
Bioconjug Chem
; 25(8): 1421-7, 2014 Aug 20.
Article
em En
| MEDLINE
| ID: mdl-25010569
ABSTRACT
To increase the affinities of antibodies or aptamers for their targets, we designed antibody-aptamer pincers (AAPs) or heterodimers for thrombin or human epidermal growth factor 2 (HER2) as a model system. For this purpose, we first conjugated a 15-mer or 29-mer anti-thrombin aptamer, which are well-known to bind to thrombin in two specific epitopes, with an anti-thrombin antibody to enable each binding part of the AAP to simultaneously recognize a different part of the thrombin molecule. The AAP comprising a 15-mer aptamer and an anti-thrombin antibody has an apparent dissociation constant (Kd(app)) value of 567 pM, and this value is approximately 1/100 of that of the antibody alone or 1/35 of that of the aptamer monomer alone. The AAP comprising a 29-mer aptamer and an anti-thrombin antibody has a much lower Kd(app) value than that of 15-mer aptamer-conjugated antibody. Furthermore, this concept of the AAP system was employed to HER2-targeted drug delivery system (DDS) based on both antibody and drug-loaded aptamer. Anti-HER2 aptamer was conjugated with anti-HER2 antibody and loaded with doxorubicin, and the resulting AAP-HER2-Dox was found to have approximately 3- and 6-fold higher cytotoxicity than drug alone and antibody alone, respectively. Therefore, this novel AAP system constructed by conjugation of the antibody with the aptamer can effectively improve the affinities of the resulting AAPs for their target molecules and the drug-loaded AAP system can possibly serve as a platform for targeted DDS against many malignancies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aptâmeros de Nucleotídeos
/
Anticorpos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioconjug Chem
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Coréia do Sul