FIG. 1.

CNTO736 has improved activity relative to constructs lacking a linker. A: The schematic outlines the structure of CNTO736 including the CH2 and CH3 domains of the Fc, the hinge including the disulfide bonds, a linker containing a partial VH region, and two GLP-1 peptides. The amino acid sequence of CNTO736 beginning at the NH₂-terminus is as follows: HSEGTFTSDVSSYLEGQAAKEFIAWLVKGRGGGSGGGSGTLVTVSSESKYGPPCPPCPAPEAA… Fc B. The concentration of cAMP was measured in INS-1E cells after addition of increasing concentrations of CNTO736 or a molecule lacking the hinge. The fit to the CNTO736 data provided an EC₅₀ of 1.8 nmol/l. C: Fasted mice (DIO, n = 5) were dosed intravenously with vehicle (▪), CNTO736 (0.5 mg/kg) (♦), or a construct lacking a hinge (0.5 mg/kg) (○) 10 min before an ipGTT. The results are presented as the means ± SE (n = 5).