Chirality in amino acids beyond the C_α configuration.

Area of Science:

• Structural chemistry
• Organic chemistry
• Biochemistry

Background:

• Chirality is fundamental to amino acids and their biological functions.
• Previous work established a chirality chain for alanine.
• Understanding chirality in natural amino acids is crucial for molecular recognition and drug design.

Purpose of the Study:

• To extend the concept of the chirality chain to all 19 natural amino acids.
• To investigate the conformational preferences and structural distortions induced by chirality.
• To analyze the stereochemical consequences of modifications at the carboxylic group.

Main Methods:

• Meta-analysis of 1179 crystal structures from the Cambridge Structural Database (CSD).
• Analysis of protonated, esterified, and carboxylate-coordinated amino acid derivatives.
• Examination of stereochemical relationships between the alpha-carbon configuration and carboxylic group conformations.

Main Results:

• The chirality chain model, previously shown for alanine, is applicable to all 19 natural amino acids.
• High diastereoselectivity is observed in the induction of -ψ and +ψ conformations from the L-configuration at Cα.
• The planar carboxylic group is distorted into asymmetric tetrahedra, confirming the integral role of the chirality chain.

Conclusions:

• The chirality chain is an inherent feature of natural amino acids, influencing their three-dimensional structures.
• This extended understanding of amino acid stereochemistry has implications for fields like medicinal chemistry and materials science.
• The study provides a unified stereochemical framework for natural amino acids.