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Published on: August 1, 2018
Effect of thioxopeptide bonds on alpha-helix structure and stability
Andreas Reiner1, Dirk Wildemann, Gunter Fischer
1Chemistry Department, Institute for Biophysical Chemistry, Technische Universität München and Munich Center for Integrated Protein Science, Lichtenbergstrasse 4, D-85747 Garching, Germany.
Journal of the American Chemical Society
|June 3, 2008
Summary
Thioxoamide bonds destabilize alpha-helices in peptides, similar to glycine substitutions. However, these modified peptide bonds are tolerated within helical structures.
Area of Science:
- Biochemistry
- Structural Biology
- Chemical Biology
Background:
- Thioxoamide (thioamide) bonds are peptide bond analogs with distinct hydrogen-bonding and photophysical properties.
- These modified bonds are suitable for studying peptide and protein physicochemical properties.
- The impact of thioxoamides on protein structure and stability remains largely uninvestigated.
Purpose of the Study:
- To experimentally determine the influence of single thioxoamide bonds on alpha-helix structure and stability in model peptides.
- To compare the helix-destabilizing effects of thioxoamide incorporation with known structural perturbations.
Main Methods:
- Circular dichroism spectroscopy to assess secondary structure and stability.
- Nuclear magnetic resonance (NMR) spectroscopy to characterize local structure and hydrogen bonding.
Main Results:
- Thioxoamide incorporation significantly destabilizes alpha-helical structures in peptides.
- The helix destabilization caused by a single thioxoamide bond is comparable to that of an alanine-to-glycine substitution, approximately 7 kJ/mol.
- NMR analysis confirmed that the thioxopeptide moiety can be accommodated within an alpha-helix, forming an i, i+4 hydrogen bond.
Conclusions:
- Thioxoamides are potent helix-destabilizing modifications in peptides.
- The observed hydrogen bonding pattern contradicts the proposed N-terminal 3(10)-helical structure for thioxopeptides.
- Thioxoamide bonds are compatible with stable alpha-helical conformations.
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