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Human calcitonin (hCT), a hormone polypeptide with 32 residues, is secreted by the C\u2010cells of the thyroid gland. The biological function of this hormone is to regulate calcium and phosphate concentrations in the blood via several different pathways. One of these is to inhibit the activity of osteoclasts; thus, calcitonin could be used to treat osteoporosis and Paget's disease of the bone. However, hCT is prone to aggregation in aqueous solution and forms amyloid fibrils. Salmon and eel calcitonin are currently used as clinical substitutes for hCT. In a previous study, we found that the replacement of two residues at positions 12 and 17 of hCT with amino acids that appear in the salmon sequence can greatly suppress peptide aggregation. The double mutations of hCT (DM hCT) also act as good inhibitors by disrupting wild\u2010type hCT fibrillization, although the inhibition mechanism is not clear. More importantly, we demonstrated that DM hCT is biologically active in interacting with the calcitonin receptor. To further understand the inhibitory effect of DM hCT on hCT fibrillization, we created four relevant peptide fragments based on the DM hCT sequence. Our examination revealed that the formation of a helix of DM hCT was possibly a key component contributing to its inhibitory effect. This finding could help in the development of peptide\u2010based inhibitors and in understanding the aggregation mechanism of hCT.<\/jats:p>","DOI":"10.1002\/pro.4711","type":"journal-article","created":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T01:37:34Z","timestamp":1687657054000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Investigating the inhibitory property of DM hCT on hCT fibrillization via its relevant peptide fragments"],"prefix":"10.1002","volume":"32","author":[{"given":"Ya\u2010Ping","family":"Chuang","sequence":"first","affiliation":[{"name":"Department of Chemistry National Taiwan Normal University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Pei","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Chemistry National Taiwan Normal University  Taipei 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