Construction of safer hirudin-derived peptides with enhanced anticoagulant properties based on C-terminal active residue adaptation and modification.

ABSTRACT:

Introduction

Hirudin exerts anticoagulant effects by inhibiting the binding and catalytic activity of thrombin to fibrinogen. However, its rigid N-terminal region irreversibly occupies the thrombin catalytic center, raising concerns about potential bleeding.

Objectives

In this study, a novel lead compound, WPHVC_V1, which is based on the competitive binding mechanism of the hirudin variant WPHV_C, was developed and validated for in vitro and in vivo activity and safety.

Methods

Saturation mutagenesis, molecular dynamics simulations and mutant protein activity assays were used to elucidate the competitive anticoagulant mechanism between WPHV_C and thrombin. Next, a recombinantly expressed tyrosylprotein sulfotransferase was used to modify and confirm the sulfation site

SUBMITTER: Yi X 

PROVIDER: S-EPMC12869248 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature