کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5621877 | 1579187 | 2017 | 8 صفحه PDF | دانلود رایگان |

- Factor XIa contributes to thrombotic disorders and is a target of therapeutic interest.
- A directed evolution approach was used to isolate RNA aptamers targeting Factor XIa.
- Two aptamers bind to anion binding and serpin binding sites on the Factor XIa catalytic domain.
- These aptamers act as noncompetitive inhibitors of Factor XIa.
BackgroundThe plasma protease factor XIa (FXIa) has become a target of interest for therapeutics designed to prevent or treat thrombotic disorders.MethodsWe 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.ResultsTwo 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.ConclusionsThe 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.
Journal: Thrombosis Research - Volume 156, August 2017, Pages 134-141