title: A chimeric analog of human and salmon calcitonin eliminates antigenicity and reduces gastrointestinal disturbances.
abstract: The minimum region in salmon calcitonin (sCT) which induces antigenicity and gastrointestinal disturbances has been identified by examining the cross-reactivity of several sCT fragments and CT analogs with antisera from sCT-treated patients, and by examining inhibition of gastrointestinal motility of these sCT fragments and CT analogs in conscious dogs. Sixteen residues at the N-terminus of sCT comprised the minimum fragment capable of inducing both activities. Human CT (hCT) showed no antigenicity and a four-order weaker inhibition of gastrointestinal motility than sCT. Based on these data, we synthesized the human and salmon chimeric CT, ACT-15, in which the 16 N-terminal residues were those of hCT and the 16 C-terminal residues were those of sCT. ACT-15 had no cross-reactivity with the antisera and had almost the same weak gastrointestinal inhibition effect as hCT in dog and rat models. Nevertheless, it retained a hypocalcemic activity and an analgesic activity comparable to sCT. These results suggest that the amino acid residues in the N-terminal half of CT are responsible for the formation of antibodies and the induction of gastrointestinal disturbances, but may not influence calcium metabolism or analgesia. Clinical studies of ACT-15 will be needed to confirm this hypothesis.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002116:Calcitonin / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D004285:Dogs; D004435:Eating / Q000187:drug effects; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000939:Epitopes; D010446:Peptide Fragments; C028815:salmon calcitonin; D002116:Calcitonin