Synthesis and biological activities of hPTH)1—34) analogues: modification of the middle part and C-terminal alkylamides

Human parathyroid hormone (hPTH) is a peptide hormone, consisting of 84 amino acid residues, which regulates calcium and phosphate ion homeostasis. The N-terminal fragment, hPTH(1–34), has been shown to possess full biological activity. The hormone is thought to have promise in the treatment of bone diseases, including osteoporosis, because of the anabolic effect which is elicited by its intermittent administration. We have already reported the recombinant synthesis of hPTH(1–84) and hPTH(1–34) [1], as well as some structureactivity relationships concerned with the chemically synthesized analogues [2]. In the present study, various hPTH(1–34) analogues were synthesized by recombinant or Fmoc-based chemical methods, and the in vitro (cAMP production in MC3T3-E1 cells) and in vivo (bone growth stimulation in 4 week old male rats) activities were evaluated.