Study summary · research use only
The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review article discusses chirality in peptide pharmaceuticals, focusing on two enantiomeric drugs: the immunostimulant Thymogen (L-Glu-L-Trp) and the immunosuppressor Thymodepressin (D-Glu(D-Trp)). The authors describe peptides' general susceptibility to proteolysis in biological systems and strategies developed to chemically increase resistance to it, noting all amino acids except glycine occur in L- and D-enantiomeric forms and that switching between forms can change a peptide's primary structure and biological activity. The review discusses Thymogen and Thymodepressin as examples of reciprocal up-and-down immune homeostasis regulation attributed to their opposite chirality, framing this as exploring chirality to bridge L- and D-biomolecule interactions, and states selected clinical results are discussed.
Abstract
Peptides show high promise in the targeting and intracellular delivery of next-generation biotherapeutics. The main limitation is peptides' susceptibility to proteolysis in biological systems. Numerous strategies have been developed to overcome this challenge by chemically enhancing the resistance to proteolysis. In nature, amino acids, except glycine, are found in L- and D-enantiomers. The change from one form to the other will change the primary structure of polypeptides and proteins and may affect their function and biological activity. Given the inherent chiral nature of biological systems and their high enantiomeric selectivity, there is rising interest in manipulating the chirality of polypeptides to enhance their biomolecular interactions. In this review, we discuss the first examples of up-and-down homeostasis regulation by two enantiomeric drugs: immunostimulant Thymogen (L-Glu-L-Trp) and immunosuppressor Thymodepressin (D-Glu(D-Trp)). This study shows the perspective of exploring chirality to remove the chiral wall between L- and D-biomolecules. The selected clinical result will be discussed.
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