Peptide and protein mimetics by retro and retroinverso analogs

Retroinverso analogs of a peptide drug or vaccine are more stable because proteases can not recognize D residues. Retroinverso analogs of a peptide can mimic functionally if the original peptide does not have significant stabilizing interactions between its side chain and backbone atoms NH and CO because these interactions are reversed in this transformation. Interaction energy analysis of original peptides structure can predict the possibility of such mimetics. Examples of successful retroinverso mimetics are mostly the peptides which has extended strand conformation.

Abstract

Retroinverso analog of a natural polypeptide can sometimes mimic the structure and function of the natural peptide. The additional advantage of using retroinverso analog is that it is resistant to proteolysis. The retroinverso analogs have peptide sequence in reverse direction with respect to natural peptide and also have chirality of amino acid inverted from L to D. The D amino acids cannot be recognized by common proteases of the body; therefore, these peptides will not be degraded easily and have a longer‐lasting effect as vaccine and inhibitor drugs. There have been many contested propositions about the geometric relationship between a peptide and its retro, inverso or retroinverso analog. A retroinverso analog sometimes fails to adopt the structure that can mimic the function of the natural peptide. In such cases, partial retroinverso analog and other modifications can help in achieving the desired structure and function. Here we review the theory, major experimental attempts, prediction methods and alternative strategies related to retroinverso peptidomimetics.

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