Abstract: The 30 amino acid peptide GLP-1 has been integrated into the stable host protein human calbindin D9k. The fusion protein binds to GLP-1R. The fusion protein agents can be useful for both diabetes treatment and GLP-1R receptor targeting MR imaging. The fusion protein comprises a first peptide that selectively binds to a site of a target cell and linked to a second peptide, where the fusion protein is more stable than the first peptide alone and may further comprise a detectable label. The first peptide of the fusion protein may be glucagon-like peptide-1 (GLP-1), glucagon-like peptide-1 (GLP-1)(7-36), or glucagon-like peptide-1 (GLP-1) (9-36), or a conservative variant thereof.

Abstract: Glucagon-like peptide-1 (GLP-1) is a member of a large family of incretin hormones secreted in nutrient-dependent response. GLP-1 acts on GLP-1 receptor (GLP-1 R) that is highly expressed on pancreatic ?-cells. The peptide has great potential for development of diabetes treatment and diagnosis. However, the pharmaceutical effects of the peptide suffer from in vivo instability and short life due to degradation by Dipeptidylpeptidase-1 (DPP-4). The 30 amino acid peptide GLP-1 has been integrated into a stable host protein human calbindin D9k. The fusion protein binds to GLP-1 R as demonstrated by immunostaining analyses of GLP-1 R expressing cells. The fusion protein agents can be useful for both diabetes treatment and GLP-1 R receptor targeting MR imaging. The fusion protein has a size about 14 kDa, which enables efficient tissue penetration and retention, and an extended circulation time, is stable, remaining intact and retaining activity after 48 hours incubation with 75% human serum.