Synthesis and Biological
Activity of Human Calcitonin Analogue
YU Chao, ZHOU Guo-Ming, LI Bo-Liang, WU Xiang-Fu and CUI
Da-Fu
( Shanghai Institute of Biochemistry, the Chinese Academy of Sciences,
Shanghai 200031, China )
Abstract The potency of salmon
calcitonin (sCT) is higher but the structural homology between sCT and human
calcition (hCT) is only 50%. Based on the comparison of the structure between
sCT and hCT, we have designed and synthesized a hCT analogue (mhCT-2) by solid phase
method, using air oxidation in diluted solution to obtain a peptide with
intramolecular disulfide bond. Through HPLC purification, we obtained a
capillary electrophoresis-homogeneous mhCT, results of analysis of its mass
spectrum and N-terminal sequencing were in accordance with the theoretical
values. The results of calcitonin bioassay by estimating the blood calcium
levels in rats showed that the potency of mhCT-2 was around 2 000 IU/mg, one
order of magnitude higher than that of hCT. In RIA assay, we have found that
the immunoactivity of mhCT-2 and hCT was much different because of their
different binding abilities to anti-hCT antibody. This indicated that the
conformation of mhCT-2 was changed as compared with hCT. In rat osteoporosis
model, the results showed that pharmacologic effects of mhCT-2 was the same as
that of sCT. The synthetic mhCT-2 seems promising to be a clinically useful
peptide with high potential in osteoporosis therapy, because it is similar in
biological properties to, but less immunogenic than sCT.
Key Words human calcitonin analogue； peptide synthesize； biological activity
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