Peptide Side-COOH Groups Have Two Distinct Conformations under Biorelevant Conditions

Area of Science:

• Biochemistry
• Chemical Physics
• Molecular Spectroscopy

Background:

• Carboxyl (COOH) groups in amino acid side chains are crucial for biochemical processes like proton transport.
• Theoretical studies suggest COOH group reactivity is conformation-dependent, but experimental data under physiological conditions is lacking.

Purpose of the Study:

• To experimentally investigate the conformational isomerism and stability of the carboxyl group in N-acetyl aspartic acid amide under aqueous conditions.
• To provide the first experimental data on COOH conformer populations in a biorelevant environment.

Main Methods:

• Utilized polarization-resolved two-dimensional infrared (2D IR) spectroscopy to probe COOH group conformations.
• Employed molecular dynamics (MD) simulations to analyze inter-molecular interactions and stability.

Main Results:

• Identified two distinct, near-planar carboxyl group conformers: syn and anti.
• Determined significant populations of both conformers in aqueous solution: 75% syn and 25% anti.
• MD simulations revealed stronger water interactions for the anti conformer, explaining its stability.

Conclusions:

• The study provides the first experimental evidence for distinct syn and anti carboxyl group conformers of N-acetyl aspartic acid amide in water.
• Conformer-specific interactions with water influence their stability and population in solution.
• These findings are critical for understanding the role of carboxyl group conformation in biochemical functions.