Site-Dependent Effect of O-Glycosylation on the Conformation and Biological Activity of Calcitonin
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- 作者：Mizuka Tagashira ; Hideki Iijima ; Yukihiro Isogai ; Masayuki Hori ; Shinji Takamatsu ; Yasuhisa Fujibayashi ; Kumiko Yoshizawa-Kumagaye ; Shuji Isaka ; Kiichiro Nakajima ; Toshihiro Yamamoto ; Tadashi Teshima
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：September 18, 2001
- 年：2001
- 卷：40
- 期：37
- 页码：11090 - 11095
- 全文大小：59K
- 年卷期：v.40,no.37(September 18, 2001)
- ISSN：1520-4995
文摘
We synthesized seven O-glycosylated calcitonin derivatives, each with a single GalNAc residueattached to either Ser or Thr, and studied their three-dimensional structure and biological activity to examinesite-dependent effects of O-glycosylation. The CD spectra in an aqueous trifluoroethanol solution showedthat the GalNAc attachment at Thr6 or Thr21 reduced the helical content of calcitonin, indicating that theO-glycosylated residue functions as a stronger helix breaker than the original amino acid residue. Onlythe GalNAc attachment at Ser2 or Thr21 retained the hypocalcemic activity of calcitonin. This resultcorresponded well to that of the calcitonin-receptor binding assay. The GalNAc attachment other thanSer2 or Thr21 perturbed the interaction with the receptor, resulting in the loss of the hypocalcemic activity.The biodistribution did not change much among the seven derivatives, but some site dependency couldalso be observed. Thus, we can conclude that the O-glycosylation affects both the conformation andbiological activity in a site-dependent manner.