Pyramidalization of the Carboxamide sp²-Center in Peptide Structures.

Area of Science:

• Structural Chemistry
• Computational Chemistry
• Biophysics

Background:

• The pyramidalization of the sp2-hybridized carboxamide group in peptides has not been previously investigated.
• Understanding peptide structure and dynamics is crucial in various biological and chemical contexts.

Purpose of the Study:

• To analyze the pyramidalization of the carboxamide group in a large dataset of peptide structures.
• To investigate the relationship between pyramidalization angle (θ) and rotation angle (ψ) around the C'-Cα bond.
• To explore the influence of amino acid side chains (R substituents) on this relationship.

Main Methods:

• Utilized a Cambridge Structural Database (CSD) search to identify 24,180 peptide structures.
• Analyzed the pyramidalization (θ) dependence on the rotation angle (ψ) using crystallographic data.
• Performed Density Functional Theory (DFT) calculations on alaninamide to support experimental findings.

Main Results:

• A unique curve with three maxima, three minima, and six zero-crossings was observed for the ψ/θ relationship.
• Individual amino acid building blocks exhibited surprisingly similar ψ/θ curves, irrespective of their R substituents.
• A rigid coupling between rotation angle (ψ) and pyramidalization (θ) was identified.

Conclusions:

• The observed consistent pyramidalization behavior is attributed to a 3-fold short-range potential originating from Cα.
• This rigid coupling dictates the degree of pyramidalization in peptides, even in solution.
• DFT calculations corroborate the crystallographic analysis, validating the proposed mechanism.