Highly potent human parathyroid hormone analogs

There is growing evidence showing that intermittent administration of human parathyroid hormone, hPTH(l-84), or its N-terminal fragment hPTH(l-34) can effectively build bone in animals and humans [1]. In an effort to develop a novel bone anabolic agent for the treatment of osteoporosis, we are involved in a search for more potent hPTH(l-34) analogs. NMR studies have indicated that in aqueous solution the major conformational features of hPTH(l-34) include two amphiphilic located at the Nand C-termini connected by a defined reverse turn region [2,3]. Our research was mainly focused on modification of residues in the hydrophobic face of the N-terminal amphiphilic in the reverse turn and at the beginning of the C-terminal