CONFORMATION OF PARATHYROID-HORMONE ANTAGONISTS BY CD, NMR, AND MOLECULAR-DYNAMICS SIMULATIONS

被引:16
作者
CHOREV, M [1 ]
BEHAR, V [1 ]
YANG, QM [1 ]
ROSENBLATT, M [1 ]
MAMMI, S [1 ]
MARETTO, S [1 ]
PELLEGRINI, M [1 ]
PEGGION, E [1 ]
机构
[1] UNIV PADUA,DEPT ORGAN CHEM,BIOPOLYMER RES CTR,I-35131 PADUA,ITALY
关键词
D O I
10.1002/bip.360360411
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:485 / 495
页数:11
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