X-aptamers: A bead-based selection method for random incorporation of druglike moieties onto next-generation aptamers for enhanced binding

By combining pseudorandom bead-based aptamer libraries with conjugation chemistry, we have created next-generation aptamers, X-aptamers (XAs). Several X-ligands can be added in a directed or random fashion to the aptamers to further enhance their binding affinities for the target proteins. Here we d...

Descripción completa

Detalles Bibliográficos
Autores: He, Weiguo, Elizondo Riojas, Miguel Angel, Li, Xin, Lokesh, Ganesh Lakshmana Rao, Somasunderam, Anoma, Thiviyanathan, Varatharasa, Volk, David E., Durland, Ross H., Englehardt, Johnnie, Cavasotto, Claudio Norberto, Gorenstein, David G.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/68063
Acceso en línea:http://hdl.handle.net/11336/68063
Access Level:acceso abierto
Palabra clave:X-Aptamers
Structure-Based Drug Design
Molecular Dynamics
Cd44
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descripción
Sumario:By combining pseudorandom bead-based aptamer libraries with conjugation chemistry, we have created next-generation aptamers, X-aptamers (XAs). Several X-ligands can be added in a directed or random fashion to the aptamers to further enhance their binding affinities for the target proteins. Here we describe the addition of a drug (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), demonstrated to bind to CD44-HABD, to a complete monothioate backbone-substituted aptamer to increase its binding affinity for the target protein by up to 23-fold, while increasing the drug's level of binding 1-million fold.