Development of a novel long-acting antidiabetic FGF21 mimetic by targeted conjugation to a scaffold antibody.

Fibroblast growth factor (FGF)21 improves insulin sensitivity, reduces body weight, and reverses hepatic steatosis in preclinical species. We generated long-acting FGF21 mimetics by site-specific conjugation of the protein to a scaffold antibody. Linking FGF21 through the C terminus decreased bioactivity, whereas bioactivity was maintained by linkage to selected internal positions.

Anti-PDGF-B monoclonal antibody reduces liver fibrosis development.

Aim:   To evaluate the usefulness of a platelet-derived growth factor (PDGF)-B specific monoclonal antibody (mAb) as a therapeutic agent to treat chronic liver fibrosis.

Methods:   Liver fibrosis was induced in ICR mice by bile duct ligation (BDL) or BALB/c mice by weekly injection of concanavalin A (ConA) for 4 or 8 weeks. A mAb specific for mouse and human PDGF-B chain, AbyD3263, was generated, tested in vitro and administered twice a week throughout the experimental period.

Two novel bovine somatotropin species generated from a common dehydroalanine intermediate.

Under stressed conditions such as prolonged exposure to high pH, the C-terminal disulfide bridge in bovine somatotropin (bST) is susceptible to a base catalyzed beta-elimination reaction. This reaction converts the disulfide bond to a dehydroalanine residue with loss of a sulphur atom. Two altered species were isolated in pure form and determined to be generated from this dehydroalanine intermediate.

Advances in protein therapeutics.

This review summarizes recent advances in the discovery and development of novel protein therapeutics. The most advanced technology platforms currently available are highlighted and examples where novel protein scaffolds have been successfully applied to identify clinical candidates are provided. This review also examines the progress of these molecules in the clinic and discusses the advantages and disadvantages of these approaches over traditional methods.

Adiponectin represses gluconeogenesis independent of insulin in hepatocytes.

Adiponectin plays important roles in regulating insulin sensitivity and atherogenesis. Adiponectin has been shown to suppress hepatic glucose production in rodents. It has not been reported whether ectopically expressed adiponectin could regulate glucose metabolism in cultured hepatocyte-like cells.