Conformation of parathyroid hormone antagonists by CD, nmr, and molecular dynamics simulations

Michael Chorev; Vered Behar; Quming Yang; Michael Rosenblatt; Stefano Mammi; Stafano Maretto; Maria Pellegrini; Evaristo Peggion

doi:10.1002/bip.360360411

Conformation of parathyroid hormone antagonists by CD, nmr, and molecular dynamics simulations

Michael Chorev^*, Vered Behar, Quming Yang, Michael Rosenblatt, Stefano Mammi, Stafano Maretto, Maria Pellegrini, Evaristo Peggion

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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, Lys¹¹ 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 were utilized in restrained distance geometry and molecular dynamics simulations. Both peptides adopt a helical C‐terminal conformation, which seems more stable in the case of the PTHrP analogue. A type II′ β‐turn centered around D‐Trp¹² and Lys¹³ is present inboth structures. © 1995 John Wiley & Sons, Inc.

Original language	English
Pages (from-to)	485-495
Number of pages	11
Journal	Biopolymers
Volume	36
Issue number	4
DOIs	https://doi.org/10.1002/bip.360360411
State	Published - Oct 1995
Externally published	Yes

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title = "Conformation of parathyroid hormone antagonists by CD, nmr, and molecular dynamics simulations",

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, Lys11 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 were utilized in restrained distance geometry and molecular dynamics simulations. Both peptides adopt a helical C‐terminal conformation, which seems more stable in the case of the PTHrP analogue. A type II′ β‐turn centered around D‐Trp12 and Lys13 is present inboth structures. {\textcopyright} 1995 John Wiley \& Sons, Inc.",

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AU - Chorev, Michael

AU - Behar, Vered

AU - Yang, Quming

AU - Rosenblatt, Michael

AU - Mammi, Stefano

AU - Maretto, Stafano

AU - Pellegrini, Maria

AU - Peggion, Evaristo

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AB - 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, Lys11 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 were utilized in restrained distance geometry and molecular dynamics simulations. Both peptides adopt a helical C‐terminal conformation, which seems more stable in the case of the PTHrP analogue. A type II′ β‐turn centered around D‐Trp12 and Lys13 is present inboth structures. © 1995 John Wiley & Sons, Inc.

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Conformation of parathyroid hormone antagonists by CD, nmr, and molecular dynamics simulations

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