The conformation of two highly potent parathyroid hormone (PTH) antagonists was investigated in water /2,2, 2-trifluoroethanol mixtures. The two peptides are derived from the sequence (7-34) of PTH and of PTH-related protein (PTHrP) and have a D-Trp replacing Gly in position 12. In the analogue derived from PTHrP, Lys(11) was replaced by Leu to remove the residual agonist activity. The study was conducted by CD and two-dimensional proton magnetic resonance spectroscopy and the nuclear Overhauser effects found weve utilized in restrained distance geometry and molecular dynam ics simulations. Both peptides adopt a helical C-terminal conformation, which seems move stable in the case of the PTHrP analogue. A type II' beta-turn centered around D-Trp(12) and Lys(13) is present in both structures. (C) 1995 John Wiley & Sons, Inc.
Conformation of Parathyroid-hormone Antagonists By Cd, Nmr, and Molecular-dynamics Simulations
MAMMI, STEFANO;MARETTO, STEFANO;PEGGION, EVARISTO
1995
Abstract
The conformation of two highly potent parathyroid hormone (PTH) antagonists was investigated in water /2,2, 2-trifluoroethanol mixtures. The two peptides are derived from the sequence (7-34) of PTH and of PTH-related protein (PTHrP) and have a D-Trp replacing Gly in position 12. In the analogue derived from PTHrP, Lys(11) was replaced by Leu to remove the residual agonist activity. The study was conducted by CD and two-dimensional proton magnetic resonance spectroscopy and the nuclear Overhauser effects found weve utilized in restrained distance geometry and molecular dynam ics simulations. Both peptides adopt a helical C-terminal conformation, which seems move stable in the case of the PTHrP analogue. A type II' beta-turn centered around D-Trp(12) and Lys(13) is present in both structures. (C) 1995 John Wiley & Sons, Inc.
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