Design and application of antibody cysteine variants.
Bioconjug Chem
; 21(2): 385-92, 2010 Feb 17.
Article
en En
| MEDLINE
| ID: mdl-20092294
ABSTRACT
Antibodies are multidomain proteins that are extensively used as a research tool in molecular biology and as therapeutics in medicine. In many cases, antibodies are engineered to contain surface cysteines for the site-specific conjugation of payloads. These antibodies can serve as payload vehicles in targeting a diseased cell to which the conjugated molecules exercise their activity. Here, we design and analyze a set of fourteen new IgG1 cysteine variants, with at least one variant per immunoglobulin fold domain. The cross-linking propensity of these mutants correlates very well with a tool we have developed for measuring aggregation propensity in silico, called spatial aggregation propensity (SAP). Our results indicate the utility of the SAP technology in selecting antibody cysteine variants with desired properties. Moreover, the different oligomerization propensity of the variants suggests a variety of applications in molecular biology and medicine, such as payload delivery, structural analysis, electrophoresis, and chromatography.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ingeniería de Proteínas
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Cisteína
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Anticuerpos Monoclonales
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Mutación
Límite:
Humans
Idioma:
En
Revista:
Bioconjug Chem
Asunto de la revista:
BIOQUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos