Generation and characterization of aptamers targeting factor XIa.
Thromb Res
; 156: 134-141, 2017 Aug.
Article
en En
| MEDLINE
| ID: mdl-28644959
ABSTRACT
BACKGROUND:
The plasma protease factor XIa (FXIa) has become a target of interest for therapeutics designed to prevent or treat thrombotic disorders.METHODS:
We used a solution-based, directed evolution approach called systematic evolution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers that target the FXIa catalytic domain.RESULTS:
Two aptamers, designated 11.16 and 12.7, were identified that bound to previously identified anion binding and serpin bindings sites on the FXIa catalytic domain. The aptamers were non-competitive inhibitors of FXIa cleavage of a tripeptide chromogenic substrate and of FXIa activation of factor IX. In normal human plasma, aptamer 12.7 significantly prolonged the aPTT clotting time.CONCLUSIONS:
The results show that novel inhibitors of FXIa can be prepared using SELEX techniques. RNA aptamers can bind to distinct sites on the FXIa catalytic domain and noncompetitively inhibit FXIa activity toward its primary macromolecular substrate factor IX with different levels of potency. Such compounds can be developed for use as therapeutic inhibitors.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor XIa
/
Aptámeros de Nucleótidos
/
Anticoagulantes
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Thromb Res
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos