Contribution of Conformationally Constrained Calcitonin (Ct) Analogs to the Understanding of the Structural and Conformational Requirements of Calcitonin Bioactivity and to the Design of Potent Agonists

Abstract

Restricting the conformational flexibility of medium-sized linear polypeptides is a valuable approach to identify and characterize the structural and conformational features that define their biological activities and to design analogs with enhanced agonistic or antagonistic properties and with potential therapeutic applications. The calcium-regulating and bone resorption-inhibiting hormone calcitonin (Ct) is a conformationally flexible polypeptide of 32 amino acid residues that has long been applied therapeutically for the treatment of osteoporosis and other bone disorder diseases. This review describes studies on the structural and conformational features of the Ct sequence that are relevant for Ct bioactivity and focuses on research work performed on rationally designed conformationally constrained Ct analogs as tools for the understanding of the molecular basis of Ct bioactivity and as potential candidates or lead structures for novel Ct-based bone disorder therapeutics.