E-viri
Recenzirano
-
Cheng, Hao; Cao, Xianhua; Xian, Ming; Fang, Lanyan; Cai, Tingwei Bill; Ji, Jacqueline Jia; Tunac, Josefino B; Sun, Duxin; Wang, Peng George
Journal of medicinal chemistry, 01/2005, Letnik: 48, Številka: 2Journal Article
Geldanamycin (GA) is a potent anticancer antibiotic that inhibits Hsp90. Its potential clinical utility is hampered by its severe toxicity. To alleviate this problem, we synthesized a series of carbohydrate−geldanamycin conjugates for enzyme-specific activation to increase tumor selectivity. The conjugation was carried out at the C-17-position of GA. Their anticancer activity was tested in a number of cancer cell lines. The enzyme-specific activation of these conjugates was evaluated with β-galactosidase and β-glucosidase. Evidently, glycosylation of C-17-position converted GA to an inactive prodrug before enzyme cleavage. Glucose−GA, as positive control, showed anticancer activity with IC50 of 70.2−380.9 nM in various cancer cells by β-glucosidase activation inside of the tumor cells, which was confirmed by 3-fold inhibition using β-glucosidase specific inhibitor 2,5-dihydroxymethy-3,4-dihydroxypyrrolidine (DMDP). Compared to glucose−GA, galactose− and lactose−GA conjugates exhibited much less activity with IC50 greater than 8000−25 000 nM. However, when galactose− and lactose−GA were incubated with β-galactosidase in the cells, their anticancer activity was enhanced by 3- to 40-fold. The results suggest that GA can be inactivated by glycosylation of C-17-position and reactivated for anticancer activity by β-galactosidase. Therefore, galactose−GA can be exploited in antibody-directed enzyme prodrug therapy (ADEPT) with β-galactosidase for enzyme-specific activation in tumors to increase tumor selectivity.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.