Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides

Abstract

The oral delivery of peptide pharmaceuticals has long been a fundamental challenge in drug development. A new chemical platform was designed based on branched piperazine-2,5-diones for creating orally available biologically active peptidomimetics. The platform includes a bio-carrier with “built-in” functionally active peptide fragments or bioactive molecules that are covalently attached via linkers. The developed platform allows for a small peptide to be taken with a particular biological activity and to be transformed into an orally stable compound displaying the same activity. Based on this approach, various peptidomimetics exhibiting hemostimulating, hemosuppressing, and adjuvant activity were prepared. In addition, new examples of a rare phenomenon when enantiomeric molecules demonstrate reciprocal biological activity are presented. Finally, the review summarizes the evolutionary approach of the short peptide pharmaceutical development from the immunocompetent organ separation to orally active cyclopeptides and peptidomimetics.

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples

“…Experimental data on Thymogen are in the scope of published data for other peptide immunomodulators. This helped us determine its application's niche in clinical practice [78,79]. Thymogen ® is registered in the Russian Ministry of Health Registration Certificate № P N002408/01 from 10.06.2009.…”