d-Amino acids in aged proteins: Analysis and biological relevance

Homochirality is essential for life. l-Amino acids are exclusively used as substrates for the polymerization and formation of peptides and proteins in living systems. However, d-amino acids, which are enantiomers of l-amino acids, were recently detected in various living organisms in the form of free d-amino acids and d-amino acid residues in peptides and proteins. In particular, d-aspartyl (Asp) residues have been detected in various proteins from diverse tissues of elderly individuals. Here, we describe three important aspects of our research: (i) a method for detecting d-β-Asp at specific sites in particular proteins, (ii) a likely spontaneous mechanism by which Asp residues in proteins invert and isomerize to the d-β-form with age under physiological conditions, (iii) a discussion of factors that favor such a reaction.