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Synthesis and Characterization of Functionalized Metal-organic Frameworks
Published on: September 5, 2014
Probing helix formation in unsolvated peptides.
Gary A Breaux1, Martin F Jarrold
1Chemistry Department, Indiana University, 800 East Kirkwood Avenue, Bloomington, IN 47405-7102, USA.
Journal of the American Chemical Society
|August 28, 2003
Summary
Adjacent alanine residues in glycine-based peptides significantly influence helix formation. Peptides with clustered alanines exhibit higher helix content, suggesting they promote helix nucleation.
Area of Science:
- Biophysical Chemistry
- Peptide Chemistry
- Structural Biology
Background:
- Understanding peptide secondary structure formation, particularly alpha-helix, is crucial in molecular biology and drug design.
- Unsolvated peptides provide a simplified system to study intrinsic folding propensities, free from solvent effects.
- Glycine-based peptides offer a unique structural scaffold due to glycine's flexibility.
Purpose of the Study:
- To investigate the impact of alanine residue positioning on helix formation in unsolvated glycine-based peptides.
- To quantify helix abundance as a function of alanine sequence in Ac-[12G3A]K+H+ isomers.
- To evaluate the applicability of Lifson-Roig theory in predicting helix formation for these specific peptides.
Main Methods:
- Ion mobility measurements were employed to analyze the gas-phase structures of nine sequence isomers of Ac-[12G3A]K+H+.
- Two distinct metrics were used to quantify the helical content within each peptide.
- Modified Lifson-Roig theory was applied to model and compare with experimental helix abundances.
Main Results:
- Helix abundance in unsolvated peptides is highly dependent on the proximity and location of three alanine residues.
- Peptides featuring three adjacent alanines demonstrated the highest helix abundances.
- Peptides with well-separated alanines showed the lowest helix abundances, deviating from theoretical predictions.
- Modified Lifson-Roig theory provided a reasonable fit for most peptides but failed to capture key experimental observations.
Conclusions:
- Adjacent alanine residues act as nucleation sites, significantly promoting alpha-helix formation in these peptides.
- The sequence-dependent helical propensity observed highlights the importance of local residue interactions in peptide folding.
- Current theoretical models like Lifson-Roig theory may require refinement to fully account for specific residue-driven nucleation effects in peptide secondary structure.
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