Abstract
The Middle Asian tortoise Testudo horsfieldii is one of the most radioresistant animals, with Lethal Dose (LD) 50/30 around 500 Gy. Extracts were prepared from different organs of the tortoise, and their biological activity was evaluated. Crude extract from the spleen was found to significantly increase survival of mice treated with lethal doses of radiation. In an iterative process, the active extract was purified by chromatography, and the fractions were screened for biological activity. Various vital parameters were monitored: peripheral blood leukocytes, spleen colonies, mitosis in the bone marrow, and survival after 30 days. The process concluded with the isolation, characterization, and synthesis of the tetrapeptide FTGN, which accelerated repopulation of the irradiated bone marrow at very low concentrations both in vivo and ex vivo. A fluorescently labeled derivative of the peptide was found to selectively associate to CD34+ stem cells, suggesting that the peptide mediates their proliferation and allows fast repopulation of hematopoietic lineages. Interestingly, the peptide protected animals from alopecia. The studies in experimental animals suggest that treatment with FTGN can potentially benefit patients who suffer bone marrow damage due to radiotherapy or chemotherapy and patients undergoing autologous or allogenic bone marrow transplantation.
| Original language | English |
|---|---|
| Article number | e3202 |
| Journal | Journal of Peptide Science |
| Volume | 25 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2019 |
Bibliographical note
Publisher Copyright:© 2019 European Peptide Society and John Wiley & Sons, Ltd.
Funding
We are grateful to Prof. Eitan Fibach of the Department of Hematology at the Hadassah Medical Center for providing equipment from his laboratory. Some of the presented results were obtained thanks to a grant provided by the Ministry of Science of the State of Israel. We are indebted to the Marcus Center of Medicinal Chemistry in Bar Ilan University and to Dr. Yuval Elias for critical reading and editing of the manuscript. Finally, we wish to express a deep gratitude for the long-term financial support and posthumously dedicate this work to Yigal Arnon. We are grateful to Prof. Eitan Fibach of the Department of Hematology at the Hadassah Medical Center for providing equipment from his laboratory. Some of the presented results were obtained thanks to a grant provided by the Ministry of Science of the State of Israel. We are indebted to the Marcus Center of Medicinal Chemistry in Bar Ilan University and to Dr. Yuval Elias for critical reading and editing of the manuscript. Finally, we wish to express a deep gratitude for the long‐term financial support and posthumously dedicate this work to Yigal Arnon.
| Funders | Funder number |
|---|---|
| Marcus Center of Medicinal Chemistry in Bar Ilan University | |
| Ministry of Science of the State of Israel |
Keywords
- bone marrow
- hematopoiesis
- irradiation
- mice
- peptide
- spleen
- tortoise
- transplantation