Design, synthesis and crystallization of a novel glucagon analog as a therapeutic agent.

Glucagon and glucagon-like peptide 1 (GLP-1) are drugs or drug candidates for the treatment of metabolic diseases such as diabetes and obesity. The native hormones have pharmacological deficiencies such as short half-life and poor solubility. A novel glucagon receptor agonist named glucagon-Cex has been designed, synthesized and crystallized. This peptide was highly soluble under physiological conditions and crystallized readily. The crystal diffracted X-rays to 2.2 A resolution and the diffraction was consistent with space group P23, with unit-cell parameters a = b = c = 48.20 A, alpha = beta = gamma = 90.0 degrees. The crystals were suitable for a full structural determination to reveal the conformational differences between glucagon-Cex and the native hormone.