Synthesis and conformational study of truncated human calcitonin analogs
Abstract
Calcitonin is a peptide hormone of 32 residues that plays a pivotal role in calcium-phosphorous metabolism; it is also believed to be a neuromodulator and/or neurotransmitter. In assays of certain in vivo hypocalcemic effects of calcitonins, the salmon and eel analogues are the most potent; human calcitonin (hCt) is among the least potent (100 times less potent than that of naturally occurring salmon or eel). Recent studies of the hypocalcemic effects of side-chained linked, cyclic human calcitonin analogues indicate that the residues at positions 17-21 play a pivotal role in determining this bioactivity of calcitonin. The cyclic nature of the peptide stabilizes the hypothesized β-turn at residues 18-19. The aim of this study is to understand the conformational requirements of synthesized hCT analogues in determining their hypocalcemic effects. Therefore, we are synthesizing truncated versions of these cyclic analogues for conformation studies in solution by nuclear magnetic resonance (NMR).