Definition
Every standard amino acid except glycine is chiral and exists in L and D forms that are mirror images. Proteins made by ribosomes use L-amino acids almost exclusively, and most proteases recognise only L-configured bonds. Substituting one or more D-amino acids into a synthetic peptide can therefore slow enzymatic breakdown and extend half-life in plasma or tissue models. D-substitution also changes local conformation, which may raise, lower or abolish receptor activity. Examples include the D-Phe and D-Trp residues in many somatostatin and GHRP analogues. Retro-inverso peptides take the idea further, using all-D residues in reversed order, as in FOXO4-DRI. Racemisation during synthesis can create unintended D-isomers, detectable by chiral analysis.