title: Biologically active, derivatizable salmon calcitonin analog: design, synthesis, and applications.
abstract: An analog of salmon calcitonin (sCT) has been synthesized, substituting Arg at positions 11 and 18 and Lys at position 14 to provide a free amino group for derivatization. The potency of [Arg11,18,Lys14]sCT was equivalent to that of sCT in activating adenylate cyclase in UMR 106-06 cells. The analog was derivatized with biotin, fluorescein, or 4-azidobenzoate without loss of activity. The derivatized analog was not degraded by lysine-specific endoprotease, whereas the underivatized [Arg11,18,Lys14]sCT was cleaved at Lys-14. The derivatized analogs were purified by HPLC and subsequently shown to possess full biological activity. The photoactive analog was used to photolabel 88,000 and 71,000 mol wt components of the calcitonin receptor in rat osteoclasts, but only an 88,000 mol wt component was photolabeled in the UMR 106-06 cells.
authors.affiliation: Department of Medicine, University of Melbourne, Repatriation General Hospital, Heidelberg, Victoria, Australia.
authors.forename: C S
authors.initials: CS
authors.lastname: D'Santos
authors.forename: G C
authors.initials: GC
authors.lastname: Nicholson
authors.forename: J M
authors.initials: JM
authors.lastname: Moseley
authors.forename: T
authors.initials: T
authors.lastname: Evans
authors.forename: T J
authors.initials: TJ
authors.lastname: Martin
authors.forename: B E
authors.initials: BE
authors.lastname: Kemp
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002116:Calcitonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D007202:Indicators and Reagents; D007700:Kinetics; D010010:Osteoclasts / Q000187:drug effects*; D051381:Rats; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012474:Salmon
chemical_list: D007202:Indicators and Reagents; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; C056877:calcitonin, salmon, Arg(11,18)-Lys(14)-; D002116:Calcitonin; D000262:Adenylyl Cyclases