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Conformation of parathyroid hormone antagonists by CD, nmr, and molecular dynamics simulations
Author(s) -
Chorev Michael,
Behar Vered,
Yang Quming,
Rosenblatt Michael,
Mammi Stefano,
Maretto Stafano,
Pellegrini Maria,
Peggion Evaristo
Publication year - 1995
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360360411
Subject(s) - chemistry , molecular dynamics , parathyroid hormone , dynamics (music) , computational chemistry , calcium , organic chemistry , physics , acoustics
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 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 ‐Trp 12 and Lys 13 is present inboth structures. © 1995 John Wiley & Sons, Inc.