TY - JOUR
T1 - Conformation and dynamics of a cyclic disulfide-bridged peptide
T2 - Effects of temperature and solvent
AU - Li, Fee
AU - Bravo-Rodriguez, Kenny
AU - Phillips, Charlotte
AU - Seidel, Rüdiger W.
AU - Wieberneit, Florian
AU - Stoll, Raphael
AU - Doltsinis, Nikos L.
AU - Sanchez-Garcia, Elsa
AU - Sander, Wolfram
PY - 2013/4/4
Y1 - 2013/4/4
N2 - The cyclic disulfide-bridged tetrapeptide cyclo(Boc-Cys-Pro-Gly-Cys-OMe) (1) was designed as a model for the study of solvent-driven conformational changes in peptides. The three-dimensional structure and dynamics of 1 were studied using a variety of experimental and computational techniques. The crystal structure of 1 reveals a β-turn stabilized by a hydrogen bond between the two cysteine residues. In solution, the UV-CD and NMR analysis of 1 suggest a β-turn II conformation, stable up to 60 C. The characteristic NMR 13C shifts of the Cβ and Cγ atoms of proline show that the peptide adopts exclusively the energetically favored trans conformation of the peptidyl-prolyl bond. The combination of IR spectroscopy with Car-Parrinello MD simulations and DFT calculations allowed us to assign the absorptions in the amide I region to the individual amino acids. The NH group of Gly, which as hydrogen bond donor competes with the NH group of Cys4 for the carbonyl oxygen atom of Cys1 as hydrogen bond acceptor, plays a relevant role for the structure and spectroscopic properties of the peptide. Since Gly is more exposed to the solvent, its hydrogen-bonding capability can be partially blocked by external solvent molecules in solution or by a second peptide molecule in the crystal. Furthermore, the presence of only one molecule of acetonitrile is sufficient to change the preferred conformation of 1, and even in acetonitrile solution the simulations suggest that on average only one solvent molecule strongly interacts with the cyclic core of the peptide.
AB - The cyclic disulfide-bridged tetrapeptide cyclo(Boc-Cys-Pro-Gly-Cys-OMe) (1) was designed as a model for the study of solvent-driven conformational changes in peptides. The three-dimensional structure and dynamics of 1 were studied using a variety of experimental and computational techniques. The crystal structure of 1 reveals a β-turn stabilized by a hydrogen bond between the two cysteine residues. In solution, the UV-CD and NMR analysis of 1 suggest a β-turn II conformation, stable up to 60 C. The characteristic NMR 13C shifts of the Cβ and Cγ atoms of proline show that the peptide adopts exclusively the energetically favored trans conformation of the peptidyl-prolyl bond. The combination of IR spectroscopy with Car-Parrinello MD simulations and DFT calculations allowed us to assign the absorptions in the amide I region to the individual amino acids. The NH group of Gly, which as hydrogen bond donor competes with the NH group of Cys4 for the carbonyl oxygen atom of Cys1 as hydrogen bond acceptor, plays a relevant role for the structure and spectroscopic properties of the peptide. Since Gly is more exposed to the solvent, its hydrogen-bonding capability can be partially blocked by external solvent molecules in solution or by a second peptide molecule in the crystal. Furthermore, the presence of only one molecule of acetonitrile is sufficient to change the preferred conformation of 1, and even in acetonitrile solution the simulations suggest that on average only one solvent molecule strongly interacts with the cyclic core of the peptide.
UR - http://www.scopus.com/inward/record.url?scp=84875791376&partnerID=8YFLogxK
U2 - 10.1021/jp4007334
DO - 10.1021/jp4007334
M3 - Article
AN - SCOPUS:84875791376
SN - 1520-6106
VL - 117
SP - 3560
EP - 3570
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 13
ER -