Development of novel activin-targeted therapeutics.

ABSTRACT: Soluble activin type II receptors (ActRIIA/ActRIIB), via binding to diverse TGF-β proteins, can increase muscle and bone mass, correct anemia or protect against diet-induced obesity. While exciting, these multiple actions of soluble ActRIIA/IIB limit their therapeutic potential and highlight the need for new reagents that target specific ActRIIA/IIB ligands. Here, we modified the activin A and activin B prodomains, regions required for mature growth factor synthesis, to generate specific activin antagonists. Initially, the prodomains were fused to the Fc region of mouse IgG2A antibody and, subsequently, "fastener" residues (Lys(45), Tyr(96), His(97), and Ala(98); activin A numbering) that confer latency to other TGF-β proteins were incorporated. For the activin A prodomain, these modificat

SUBMITTER: Chen JL 

PROVIDER: S-EPMC4351455 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature