Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK
Thymosin α1 (Tα1), is a peptidic hormone, whose immune regulatory properties have been demonstrated both in vitro and in vivo and approved in different countries for treatment of several viral infections and cancers. Tα1 assumes a conformation in negative membranes upon insertion into the phosphatid...
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MDPI AG
2017-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/22/11/1843 |
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| author | Walter Mandaliti Ridvan Nepravishta Francesca Pica Paola Sinibaldi Vallebona Enrico Garaci Maurizio Paci |
| author_facet | Walter Mandaliti Ridvan Nepravishta Francesca Pica Paola Sinibaldi Vallebona Enrico Garaci Maurizio Paci |
| author_sort | Walter Mandaliti |
| collection | DOAJ |
| description | Thymosin α1 (Tα1), is a peptidic hormone, whose immune regulatory properties have been demonstrated both in vitro and in vivo and approved in different countries for treatment of several viral infections and cancers. Tα1 assumes a conformation in negative membranes upon insertion into the phosphatidylserine exposure as found in several pathologies and in apoptosis. These findings are in agreement with the pleiotropy of Tα1, which targets both normal and tumor cells, interacting with multiple cellular components, and have generated renewed interest in the topic. Hyaluronan (HA) occurs ubiquitously in the extracellular matrix and on cell surfaces and has been related to a variety of diseases, and developmental and physiological processes. Proteins binding HA, among them CD44 and the Receptor for HA-mediated motility (RHAMM) receptors, mediate its biological effects. NMR spectroscopy indicated preliminarily that an interaction of Tα1 with HA occurs specifically around lysine residues of the sequence LKEKK of Tα1 and is suggestive of a possible interference of Tα1 in the binding of HA with CD44 and RHAMM. Further studies are needed to deepen these observations because Tα1 is known to potentiate the T-cell immunity and anti-tumor effect. The binding inhibitory activity of Tα1 on HA-CD44 or HA-RHAMM interactions can suppress both T-cell reactivity and tumor progression. |
| first_indexed | 2024-12-22T02:21:11Z |
| format | Article |
| id | doaj.art-bf401fe68c9f4ec7b91975f4c27f88cc |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T02:21:11Z |
| publishDate | 2017-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-bf401fe68c9f4ec7b91975f4c27f88cc2022-12-21T18:42:08ZengMDPI AGMolecules1420-30492017-10-012211184310.3390/molecules22111843molecules22111843Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKKWalter Mandaliti0Ridvan Nepravishta1Francesca Pica2Paola Sinibaldi Vallebona3Enrico Garaci4Maurizio Paci5Department of Chemical Sciences and Technologies, University of Rome “Tor Vergata”, via della Ricerca Scientifica 1, 00133 Rome, ItalyDepartment of Chemical Sciences and Technologies, University of Rome “Tor Vergata”, via della Ricerca Scientifica 1, 00133 Rome, ItalyDepartment of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, via Montpellier 1, 00133 Rome, ItalyDepartment of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, via Montpellier 1, 00133 Rome, ItalySan Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, 00163 Rome, ItalyDepartment of Chemical Sciences and Technologies, University of Rome “Tor Vergata”, via della Ricerca Scientifica 1, 00133 Rome, ItalyThymosin α1 (Tα1), is a peptidic hormone, whose immune regulatory properties have been demonstrated both in vitro and in vivo and approved in different countries for treatment of several viral infections and cancers. Tα1 assumes a conformation in negative membranes upon insertion into the phosphatidylserine exposure as found in several pathologies and in apoptosis. These findings are in agreement with the pleiotropy of Tα1, which targets both normal and tumor cells, interacting with multiple cellular components, and have generated renewed interest in the topic. Hyaluronan (HA) occurs ubiquitously in the extracellular matrix and on cell surfaces and has been related to a variety of diseases, and developmental and physiological processes. Proteins binding HA, among them CD44 and the Receptor for HA-mediated motility (RHAMM) receptors, mediate its biological effects. NMR spectroscopy indicated preliminarily that an interaction of Tα1 with HA occurs specifically around lysine residues of the sequence LKEKK of Tα1 and is suggestive of a possible interference of Tα1 in the binding of HA with CD44 and RHAMM. Further studies are needed to deepen these observations because Tα1 is known to potentiate the T-cell immunity and anti-tumor effect. The binding inhibitory activity of Tα1 on HA-CD44 or HA-RHAMM interactions can suppress both T-cell reactivity and tumor progression.https://www.mdpi.com/1420-3049/22/11/1843Thymosin α1CD44RHAMMthymic hormone |
| spellingShingle | Walter Mandaliti Ridvan Nepravishta Francesca Pica Paola Sinibaldi Vallebona Enrico Garaci Maurizio Paci Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK Molecules Thymosin α1 CD44 RHAMM thymic hormone |
| title | Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK |
| title_full | Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK |
| title_fullStr | Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK |
| title_full_unstemmed | Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK |
| title_short | Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK |
| title_sort | thymosin α1 interacts with hyaluronic acid electrostatically by its terminal sequence lkekk |
| topic | Thymosin α1 CD44 RHAMM thymic hormone |
| url | https://www.mdpi.com/1420-3049/22/11/1843 |
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