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.
Li
Pengyun
P
Department of Chemistry and Biochemistry Program, Indiana University, Bloomington, Indiana 47405, USA.
Rogers
Tanya
T
Smiley
David
D
DiMarchi
Richard D
RD
Zhang
Faming
F
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
D010446:Peptide Fragments; D005934:Glucagon