Conformation-specific RNA aptamers for phenotypic distinction between normal von Willebrand factor and type 2B von Willebrand disease.

ABSTRACT: The A1 domain in Von Willebrand Factor (VWF) initiates coagulation through binding to platelet glycoprotein GPIbα receptors. Von Willebrand Disease (VWD)-Mutations in A1 that either impair (type 2M) or enhance (type 2B) platelet adhesion to VWF can locally destabilize and even misfold the domain. We leveraged misfolding in the gain-of-function type 2B VWD phenotype as a target, distinct from the normal conformation. Two nuclease-resistant 2'-fluoropyrimidine RNA aptamers were selected to discriminate normal A1 domains from a type 2B V1314D A1 variant in a glycosylated A1A2A3 tri-domain VWF-fragment. Two aptamers, W9 and V1, were isolated that selectively recognize, bind, and inhibit the A1-GPIbα interaction with WT A1A2A3 and V1314D A1A2A3, respectively. These aptamers were tested against

SUBMITTER: Machha VR 

PROVIDER: S-EPMC11664255 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature