Chiral discrimination in the confined environment of biological nanospace: reactions and interactions involving amino acids and peptides

Although chiral discrimination in biological systems is overwhelmingly present, its molecular mechanism remained a puzzle. Why the basic blocks of life like L-amino acid and D-sugar are not being scrambled and retain enantiomeric purity since evolution is an unresolved question. In the present review we focus on the recent experimental and computational studies on the chiral discrimination in reactions such as peptide synthesis and aminoacylation. Experimental studies have shown that a clear homochiral preference exists favouring L-amino acid. Recent combined quantum mechanical/molecular mechanical studies explain the high level of stereospecificity of the processes and revealed multiple factors responsible for the discrimination and concomitant retention of the biological homochirality. Chirality of the relevant molecular segments and the intricate interaction between them as well as with the surrounding residues are important. The confinement of the chiral reactants within the biological nanospaces like the peptidyl transferase centre in tRNA and active site of the aminoacyl transferase as well as the nanoscale proximity are important for the manifestation of the discrimination. Multiple favourable influences of the stereochemistry of the natural chirality (D-form) of the sugar ring are noted. This explains the heterochiral relationship of the D-sugar and L-amino acid in biology. In addition to factors such as chirality, confinement and nanoscale proximity of the molecular segments, the network of electrostatic interaction present in the active site plays a significant role in the chiral discrimination in aminoacylation. Chiral discriminations in the biological cavities of nucleic acid and cyclodextrin are also briefly reviewed.