How Full-Length FVIII Benefits from Its Heterogeneity - Insights into the Role of the B-Domain.

ABSTRACT:

Purpose

To explore how the natural heterogeneity of human coagulation factor VIII (FVIII) and the processing of its B-domain specifically modulate protein aggregation.

Methods

Recombinant FVIII (rFVIII) molecular species containing 70% or 20% B-domain, and B-domain-deleted rFVIII (BDD-rFVIII), were separated from full-length recombinant FVIII (FL-rFVIII). Purified human plasma-derived FVIII (pdFVIII) was used as a comparator. Heterogeneity and aggregation of the various rFVIII molecular species, FL-rFVIII and pdFVIII were analysed by SDS-PAGE, dynamic light scattering, high-performance size-exclusion chromatography and flow cytometry-based particle analysis.

Results

FL-rFVIII and pdFVIII were heterogeneous in nature and demonstrated similar resistance to aggregation u

SUBMITTER: Anzengruber J 

PROVIDER: S-EPMC6443606 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature