Abstract
In nature, amino acids are found in two forms, L and D enantiomers, except for glycine which does not have a chiral center. The change of one form to the other will lead to a change in the primary structure of proteins and hence may affect the function and biological activity of proteins. Indeed, several D-amino acid-containing peptides (DAACPs) were isolated from patients with cataracts, Alzheimer’s and other diseases. Additionally, significant levels of free D-amino acids were found in several diseases, reflecting the disease conditions. Studying the molecular mechanisms of the DAACPs formation and the alteration in D-amino acids metabolism will certainly assist in understanding these diseases and finding new biomarkers and drug targets. In this review, the presence of DAACPs and free D-amino acids and their links with disease development and progress are summarized. Similarly, we highlight some recent advances in analytical techniques that led to improvement in the discovery and analysis of DAACPs and D-amino acids.
Highlights
Amino acids, the building blocks of peptides and proteins, are found naturally in two forms (L and D enantiomers), except for glycine which does not have a chiral center
The incorporation of D-amino acids in proteins may result from different mechanisms; non-enzymatic racemization linked with ageing or diseases or by enzymatic post-transnational modification (PTM) for the mRNA-encoded L-amino acids [2]
The levels of D-Ser and D-Asp were significantly higher in MCF-7 cancer cells compared to non-tumorigenic MCF-10A epithelial cells. The elevation of these D-amino acids could be a result of the upregulation of the enzyme racemases. These findings suggest possible roles of these D-amino acids in breast cancer proliferation and consider them as potential oncometabolites for breast cancer [87]
Summary
The building blocks of peptides and proteins, are found naturally in two forms (L and D enantiomers), except for glycine which does not have a chiral center. The tertiary structure of proteins is critical for their activity, a change in one amino acid stereoisomerism may lead to dramatical change in their physicochemical properties and activity. It was a long-lasting belief that only the L-forms are incorporated in the synthesis of proteins, and this homochirality of L-amino acids in protein synthesis was one of the mysteries in life. In living organisms, free forms of D-amino acids, and several D-amino acidcontaining peptides (DAACPs) have been isolated [1,2].
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