| Autor: |
Mezo, I., Lovas, S., Palyi, I., Vincze, B., Kalnay, A., Turi, G., Vadasz, Zs., Seprodi, J., Idei, M., Toth, G., Gulyas, E., Otvos, F., Mak, M., Horvath, J. E., Teplan, I., Murphy, R. F. |
| Zdroj: |
Journal of Medicinal Chemistry; October 10, 1997, Vol. 40 Issue: 21 p3353-3358, 6p |
| Abstrakt: |
Following the observation that the activity of gonadotropin-releasing hormone III (GnRH-III) in the suppression of growth of MDA-MB-231 and MCF-7 breast cancer cells surpasses that of GnRH and other analogs thereof, analogs of GnRH-III were synthesized to investigate the structural basis for the improved antitumor activity. Compounds synthesized include analogs with changes in the central sequence in which GnRH-III differs from GnRH and in the C- and N-terminal regions. The results indicate that a salt bridge between Asp6 and Lys8 stabilizes the active conformation of GnRH-III and show the importance of the Trp7. Replacement of the C-terminal Gly-NH2 with d-Ala-NH2 was not well tolerated, but replacement with ethylamide was. Replacement of pGlu1 with Ac-d-Trp appears to have a significantly deleterious effect on a unique conformation of GnRH-III which is responsible for its binding to the receptors on cancer cell lines and the resultant antitumor activity. |
| Databáze: |
Supplemental Index |
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