About D-Amino Acid Peptides
The design of all-D-peptides has been applied to increase bioactive peptides’ resistance to endogenous enzymes, as well as their bioavailability. Retro-inverso peptides are obtained by replacing the standard L-amino acid residues with the corresponding D-amino acids and reversing the direction of the peptide backbone. Therefore, the original spatial orientation and the chirality of the side chains is unchanged. This results in a non-complementary side chain topochemistry between the analog and the parental L-peptide. The significantly improved biostability of D-peptides usually leads to longer in vivo circulation half-time, making the D-peptide based drug delivery system more attractive and efficient than their L-peptide counterparts. Success has been achieved immunologically in using retro-inverso peptides toward antigenic mimicry of their parent l-peptides. It was found that the retro-all-d-peptide isomer of p53(15–29), like its parent l-peptide, adopted a right-handed helical conformation in the complex. However, in some cases, the retro-inverso isomers are significantly inferior to their parent l-peptides. The low cellular uptake of D-peptides remain an unmet challenge. So the best way is to insert some key D amino acids into the peptide sequence. For example, some pharmaceutical important peptide antibiotics such as gramicidins, actinomycins, or bacitracins incorporate D-amino acids into the drug design. The assemblies of D-peptides deserve further exploration and may lead to more surprises.
D amino acid peptide with high stability