1 H Nuclear‐Magnetic‐Resonance Studies of the Molecular Conformation of Monomeric Glucagon in Aqueous Solution

Dilute aqueous solutions of glucagon were investigated by high‐resolution 1 H nuclear magnetic resonance at 360 MHz. Monomeric glucagon was found to adopt predominantly an extended flexible conformation which contains, however, a local non‐random spatial structure involving the fragment ‐Phe‐22‐Val‐23‐Gln‐24‐Trp‐25‐. This local conformation is preserved in the partial sequence 22–26 and could thus be characterized in detail. Two interesting conclusions resulted from these experiments. One is that the local spatial structure in the fragment 22–25 of glucagon is identical to that observed in the fragment 20–23 of the human parathyroid hormone. Secondly, the backbone conformation in the C‐terminal fragment of glucagon in solution must be different from the α‐helical structure observed in single crystals of glucagon. These new structural data are analyzed with regard to relationships with glucagon binding to the target cells.