Structure-Guided Designing Pre-Organization in Bivalent Aptamers.
J Am Chem Soc
; 144(10): 4507-4514, 2022 03 16.
Article
em En
| MEDLINE
| ID: mdl-35245025
ABSTRACT
Multivalent interaction is often used in molecular design and leads to engineered multivalent ligands with increased binding avidities toward target molecules. The resulting binding avidity relies critically on the rigid scaffold that joins multiple ligands as the scaffold controls the relative spatial positions and orientations toward target molecules. Currently, no general design rules exist to construct a simple and rigid DNA scaffold for properly joining multiple ligands. Herein, we report a crystal structure-guided strategy for the rational design of a rigid bivalent aptamer with precise control over spatial separation and orientation. Such a pre-organization allows the two aptamer moieties simultaneously to bind to the target protein at their native conformations. The bivalent aptamer binding has been extensively characterized, and an enhanced binding has been clearly observed. This strategy, we believe, could potentially be generally applicable to design multivalent aptamers.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aptâmeros de Nucleotídeos
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article