Human Parathyroid Hormone (PTH) is an 84-amino acid peptide which is a major regulator of calcium homeostasis. Human Parathyroid Hormone-related Protein (PTHrP) is a 139-175 amino acid protein which plays a major role in the pathogenesis of hypercalcemia of malignancy. It has been shown that the 1-34 that the N-terminal fragments of PTH and PTHrP maintain the same biological activity of the intact, native sequences, mediated through a class II G-protein coupled receptor (PTH1 receptor). The hypothesis was made that the two fragments, in spite of the low sequence homology, share the same bioactive conformation at the receptor binding site. Previous investigations carried out on a series of biologically active and inactive PTH(1-34) and PTHrP(1-34) analog led to the hypothesis that the structural elements required for biological activity are two N-terminal and C-terminal helical segments and hinges or flexible points around positions 12 and 19. To verify this hypothesis, in the present work we synthesized and characterized three analogs of PTH(1-34) containing beta-Ala residues in positions 11, 12 and 13.

Structure-Function Relationship Studies on Parathyroid Hormone (PTH) 1-34 Analogs Containing beta-Amino Acid Residues in Positions 11, 12 and 13

PEGGION, EVARISTO;MAMMI, STEFANO;SCHIEVANO, ELISABETTA;
2001

Abstract

Human Parathyroid Hormone (PTH) is an 84-amino acid peptide which is a major regulator of calcium homeostasis. Human Parathyroid Hormone-related Protein (PTHrP) is a 139-175 amino acid protein which plays a major role in the pathogenesis of hypercalcemia of malignancy. It has been shown that the 1-34 that the N-terminal fragments of PTH and PTHrP maintain the same biological activity of the intact, native sequences, mediated through a class II G-protein coupled receptor (PTH1 receptor). The hypothesis was made that the two fragments, in spite of the low sequence homology, share the same bioactive conformation at the receptor binding site. Previous investigations carried out on a series of biologically active and inactive PTH(1-34) and PTHrP(1-34) analog led to the hypothesis that the structural elements required for biological activity are two N-terminal and C-terminal helical segments and hinges or flexible points around positions 12 and 19. To verify this hypothesis, in the present work we synthesized and characterized three analogs of PTH(1-34) containing beta-Ala residues in positions 11, 12 and 13.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2464860
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