DEGRADATION PATHWAYS OF SALMON-CALCITONIN IN AQUEOUS-SOLUTION

Salmon calcitonin (sCT), a 32-amino-acid peptide, is the active compon ent in many pharmaceuticals used for the management of bone diseases. The degradation pathways of sCT were determined, and the structures of the major degradation products were identified. Aqueous solutions of sCT at pH values of 3, 4, 5, and 6 were degraded, and the major degrad ation products were detected using reversed phase and size-exclusion h igh-performance liquid chromatography (HPLC). The degradation rate and pathways of sCT are strongly dependent on pH in the pH range between 3 and 6. The major degradation products were isolated by semipreparati ve HPLC and identified using a variety of spectroscopic and bioanalyti cal techniques. The results show that sCT can undergo hydrolyses resul ting in cleavage of the 1-2 amide bond and deamidation of the Gln(14) and Gln(20) residues, sulfide exchange that leads to an unusual trisul fide derivative, and dimerization to reducible and nonreducible dimers . The mechanisms for the pathways can be rationalized from known degra dation pathways of peptide and proteins.