التفاصيل البيبلوغرافية
| العنوان: |
Characterization of a new potent and long-lasting single chain peptide agonist of RXFP1 in cells and in vivo translational models |
| المؤلفون: |
Illiano, S, Poirier, B, Minoletti, C, Pasquier, O, Riva, L, Chenede, X, Menguy, I, Guillotel, M, Prigent, P, Le Claire, S, Gillot, F, Thill, G, Lo Presti, F, Corbier, A, Le Bail, J-C, Grailhe, P, Monteagudo, E, Ingenito, R, Bianchi, E, Philippo, C, Duclos, O, Mallart, S, Bathgate, R, Janiak, P |
| بيانات النشر: |
NATURE PORTFOLIO |
| سنة النشر: |
2022 |
| المجموعة: |
The University of Melbourne: Digital Repository |
| الوصف: |
Despite beneficial effects in acute heart failure, the full therapeutic potential of recombinant relaxin-2 has been hampered by its short half-life and the need for intravenous administration limiting its use to intensive care units. A multiparametric optimization of the relaxin B-chain led to the identification of single chain lipidated peptide agonists of RXFP1 like SA10SC-RLX with subcutaneous bioavailability and extended half-life. SA10SC-RLX has sub nanomolar activity on cells expressing human RXFP1 and molecular modeling associated with the study of different RXFP1 mutants was used to decipher the mechanism of SA10SC-RLX interaction with RXFP1. Telemetry was performed in rat where SA10SC-RLX was able to engage RXFP1 after subcutaneous administration without tachyphylaxis after repeated dosing. Renal blood flow was then used as a translational model to evaluate RXFP1 activation. SA10SC-RLX increased renal blood flow and decreased renal vascular resistance in rats as reported for relaxin in humans. In conclusion, SA10SC-RLX mimics relaxin activity in in vitro and in vivo models of acute RXFP1 engagement. SA10SC-RLX represents a new class of long-lasting RXFP1 agonist, suitable for once daily subcutaneous administration in patients and potentially paving the way to new treatments for chronic fibrotic and cardiovascular diseases. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| تدمد: |
2045-2322 |
| Relation: |
pii: 10.1038/s41598-022-24716-2; Illiano, S., Poirier, B., Minoletti, C., Pasquier, O., Riva, L., Chenede, X., Menguy, I., Guillotel, M., Prigent, P., Le Claire, S., Gillot, F., Thill, G., Lo Presti, F., Corbier, A., Le Bail, J. -C., Grailhe, P., Monteagudo, E., Ingenito, R., Bianchi, E. ,. Janiak, P. (2022). Characterization of a new potent and long-lasting single chain peptide agonist of RXFP1 in cells and in vivo translational models. SCIENTIFIC REPORTS, 12 (1), https://doi.org/10.1038/s41598-022-24716-2.; http://hdl.handle.net/11343/334589 |
| الاتاحة: |
http://hdl.handle.net/11343/334589 |
| Rights: |
CC BY ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: |
edsbas.DA30C92C |
| قاعدة البيانات: |
BASE |
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