Analogues of human parathyroid hormone (1-31)NH(2): further evaluation of the effect of conformational constraint on biological activity

• Published in: Bioorganic & medicinal chemistry Vol. 10; no. 3; pp. 731 - 736
• Main Authors: Condon, Stephen M, Darnbrough, Shelley, Burns, Christopher J, Bobko, Mark A, Morize, Isabelle, Uhl, Joanne, Jariwala, Navinchandra U, Burke, Kathleen, Labaudiniere, Richard F
• Format: Journal Article
• Language: English
• Published: England 01.03.2002
• Subjects: Adenylyl Cyclases - drug effects; Amino Acid Sequence; Animals; Humans; Lactams - chemistry; Molecular Sequence Data; Parathyroid Hormone - chemistry; Parathyroid Hormone - genetics; Parathyroid Hormone - pharmacology; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - pharmacology; Protein Binding; Protein Conformation; Protein Engineering; Rats; Receptors, Parathyroid Hormone - agonists; Structure-Activity Relationship; Tumor Cells, Cultured

A series of conformationally-restricted analogues of hPTH was prepared, based on the parent peptide agonist, cyclo(Lys(18)-Asp(22))[Ala(1),Nle(8),Lys(18),Asp(22),Leu(27)]hPTH(1-31)NH(2) (2, EC(50)=0.29nM). Truncation of 2 at either the N- or C-termini resulted in peptides with reduced agonist activi...