Synthesis of Highly Active Analogues of Salmon Calcitonin

Abstract

This chapter discusses the biochemical methods of synthesis of highly active analogs of salmon calcitonin. Following further purification by Potts and co-workers, the minor component is found to contain two different peptides with similar, but not identical, amino acid compositions. Both are linear dotriacontapeptides bearing a heptapeptidic loop closed by a disulphide bridge at its N-terminal end. Because only limited quantities of these materials are available, the elucidation of structure has to be confirmed by synthesis. On comparing the structures of the Salmon-CTs, there are obvious similarities. The amino acid sequences are nearly identical in large sections of the molecules, bearing in mind that the replacement of glutamic acid and tyrosine in positions 15 and 22 in Salmon-CT 1 by aspartic acid and phenylalanine in Salmon-CT 2 and 3 is not a significant difference. On the other hand, the replacement of valine in position 8 by methionine and the changing of the C-terminal tetrapeptide sequence in Salmon-CT 2 and 3 confer upon these molecules greater similarity to human CT. All the Salmon-CTs have two lysine residues in positions 11 and 18 and one arginine in position 24, whereas human CT possesses only one lysine residue in position 18.