Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides
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”...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/17/13534 |
| _version_ | 1797582425778290688 |
|---|---|
| author | Vladislav Deigin Natalia Linkova Olga Volpina |
| author_facet | Vladislav Deigin Natalia Linkova Olga Volpina |
| author_sort | Vladislav Deigin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T23:21:01Z |
| format | Article |
| id | doaj.art-f38ff5a1d390408495279cb52507570a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:21:01Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f38ff5a1d390408495279cb52507570a2023-11-19T08:18:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171353410.3390/ijms241713534Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based CyclopeptidesVladislav Deigin0Natalia Linkova1Olga Volpina2The Laboratory of Synthetic Vaccines of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St., 16/10, Moscow 117997, RussiaThe Research Laboratory of the Development of Drug Delivery Systems, St. Petersburg Research Institute of Phthisiopulmonology, Ligovskii Prospect, 2-4, St. Petersburg 191036, RussiaThe Laboratory of Synthetic Vaccines of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St., 16/10, Moscow 117997, RussiaThe 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.https://www.mdpi.com/1422-0067/24/17/13534immunotropic peptidesreciprocal activity peptide enantiomerscyclic peptidomimeticsdrug development |
| spellingShingle | Vladislav Deigin Natalia Linkova Olga Volpina Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides International Journal of Molecular Sciences immunotropic peptides reciprocal activity peptide enantiomers cyclic peptidomimetics drug development |
| title | Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides |
| title_full | Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides |
| title_fullStr | Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides |
| title_full_unstemmed | Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides |
| title_short | Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides |
| title_sort | advancement from small peptide pharmaceuticals to orally active piperazine 2 5 dion based cyclopeptides |
| topic | immunotropic peptides reciprocal activity peptide enantiomers cyclic peptidomimetics drug development |
| url | https://www.mdpi.com/1422-0067/24/17/13534 |
| work_keys_str_mv | AT vladislavdeigin advancementfromsmallpeptidepharmaceuticalstoorallyactivepiperazine25dionbasedcyclopeptides AT natalialinkova advancementfromsmallpeptidepharmaceuticalstoorallyactivepiperazine25dionbasedcyclopeptides AT olgavolpina advancementfromsmallpeptidepharmaceuticalstoorallyactivepiperazine25dionbasedcyclopeptides |