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Structure and folding of glucagon‐like peptide‐1‐(7–36)‐amide in aqueous trifluoroethanol studied by NMR spectroscopy
Author(s) -
Chang Xiaoqing,
Keller Danielle,
Bjørn Søren,
Led Jens J.
Publication year - 2001
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.880
Subject(s) - chemistry , random coil , aqueous solution , folding (dsp implementation) , amide , nuclear magnetic resonance spectroscopy , crystallography , helix (gastropod) , monomer , peptide , protein folding , residue (chemistry) , circular dichroism , stereochemistry , organic chemistry , biochemistry , polymer , ecology , snail , electrical engineering , biology , engineering
The conformational changes of free, monomeric glucagon‐like peptide‐1‐(7–36)‐amide (GLP‐1) in aqueous solution with increasing concentrations of 2,2,2‐trifluoroethanol (TFE) were monitored by NMR spectroscopy. It was found that GLP‐1 gradually assumes a stable, single‐stranded helical structure in water solution when the TFE concentration is increased from 0 to 35% (v/v). No further structural changes were observed at higher TFE concentrations. The structure of GLP‐1 in 35% TFE was determined from 292 distance restraints and 44 angle restraints by distance geometry, simulating annealing and restrained energy minimization. The helical structure extends from T7 to K28, with a less well‐defined region around G16 and a disordered six‐residue N‐terminal domain. The folding process of GLP‐1 from random coil (in water) to helix (in 35% TFE) is initiated by the formation of the C‐terminal segment of the helix that is extended gradually towards the N‐terminus of the peptide with increasing concentration of TFE. The exchange rates of the slow exchanging amide protons indicate that the C‐terminal part of the helix is more stable than the N‐terminal part. Copyright © 2001 John Wiley & Sons, Ltd.