Author/Authors :
Stephen M. Condon، نويسنده , , Shelley Darnbrough، نويسنده , , Christopher J. Burns، نويسنده , , Mark A. Bobko، نويسنده , , Isabelle Morize، نويسنده , , Joanne Uhl، نويسنده , , Navinchandra U Jariwala، نويسنده , , Kathleen Burke، نويسنده , , Richard F Labaudiniere، نويسنده ,
Abstract :
A series of conformationally-restricted analogues of hPTH was prepared, based on the parent peptide agonist, cyclo(Lys18-Asp22)[Ala1,Nle8,Lys18,Asp22,Leu27]hPTH(1–31)NH2 (2, EC50=0.29 nM). Truncation of 2 at either the N- or C-termini resulted in peptides with reduced agonist activity as measured by stimulation of adenylate cyclase activity in the rat osteosarcoma cell line (ROS 17/2.8). Alanine- and glycine-scanning at the N-terminus of 2 was consistent with data previously obtained on linear hPTH(1–34). Other locations within the primary sequence of hPTH(1–31)NH2 were evaluated by the placement of the [i, i+4] lactam constraining element. Ring size and lactam orientations at the 18–22 positions were also examined.
