D-amino-acid-containing Peptides

D amino acid containing peptides are peptides which are partially or entirely composed of D-amino acids. Naturally occurring proteins have traditionally been thought to be composed exclusively of amino acids in the L‐configuration, however since the 1980’s, numerous D‐amino acid containing peptides have been discovered in multicellular organisms.

D-amino acids themselves have long been known, but thought to have a minor function in biological processes. In fact D-amino acids are present in high concentrations in microorganisms, plants, mammals and humans. In mammalian brains, D-serine acts as a co-agonist of NMDA type glutamate receptors, and D-aspartate is a major regulator of adult neurogenesis.

D-peptides have become important as therapeutic agents due to their superior resistance to metabolisation by proteases and cytochrome P450 enzymes. Metabolism commonly occurs in the gastrointestinal tract, blood and liver but D-peptides are far less susceptible to degradation than L-peptides and can so be taken orally and be effective for a longer period of time. In some cases, D-peptides can have a low immunogenic response. They have found use as anticancer and anti-inflammatory agents, inhibitors of amyloidogenesis, and delivery agents.