title: Design, synthesis and crystallization of a novel glucagon analog as a therapeutic agent.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry Program, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Pengyun
authors.initials: P
authors.lastname: Li
authors.forename: Tanya
authors.initials: T
authors.lastname: Rogers
authors.forename: David
authors.initials: D
authors.lastname: Smiley
authors.forename: Richard D
authors.initials: RD
authors.lastname: DiMarchi
authors.forename: Faming
authors.initials: F
authors.lastname: Zhang
mesh_terms: D003460:Crystallization; D018360:Crystallography, X-Ray; D005934:Glucagon / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000627:therapeutic use
chemical_list: D010446:Peptide Fragments; D005934:Glucagon