SOLUTION STRUCTURE OF A HUMAN CALCITONIN ANALOG ELUCIDATED BY NMR ANDDISTANCE GEOMETRY CALCULATIONS

Three-dimensional structure of a human calcitonin analog (abbreviated as hCTa) in which the amino acids of the wild type are replaced at pos itions 12, 16 and 19 by leucine residues and further at position 22 by a tyrosine residue was studied in TFE solution by H-1-NMR and distanc e geometry calculations. This analog has a 15-20 times activity as com pared with the wild type. The amino acid replacements resulted in form ation of an amphiphilic alpha-helix in the region between the residues 4-20. The overall three-dimensional structure is similar to that of t he wild type. The conformational feature of hCTa with a hydrophobic fa ce composed with a Met and four Leu residues may be related to its hig her hypocalcemic potency. (C) Munksgaard 1995.