Novel MASP-2 inhibitors developed via directed evolution of human TFPI1 are potent lectin pathway inhibitors.

ABSTRACT: The lectin pathway (LP) of the complement system is an important antimicrobial defense mechanism, but it also contributes significantly to ischemia reperfusion injury (IRI) associated with myocardial infarct, stroke, and several other clinical conditions. Mannan-binding lectin-associated serine proteinase 2 (MASP-2) is essential for LP activation, and therefore, it is a potential drug target. We have previously developed the first two generations of MASP-2 inhibitors by in vitro evolution of two unrelated canonical serine proteinase inhibitors. These inhibitors were selective LP inhibitors, but their nonhuman origin rendered them suboptimal lead molecules for drug development. Here, we present our third-generation MASP-2 inhibitors that were developed based on a human inhibitor scaf

SUBMITTER: Szakacs D 

PROVIDER: S-EPMC6527154 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature