Inhibitors of farnesylation of Ras from a microbial natural products screening program

Citation
D. Vilella et al., Inhibitors of farnesylation of Ras from a microbial natural products screening program, J IND MIC B, 25(6), 2000, pp. 315-327
Citations number
83
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biotecnology & Applied Microbiology",Microbiology
Journal title
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
ISSN journal
1367-5435 → ACNP
Volume
25
Issue
6
Year of publication
2000
Pages
315 - 327
Database
ISI
SICI code
1367-5435(200012)25:6<315:IOFORF>2.0.ZU;2-5
Abstract
Mutant ras oncogenes are associated with various human tumors such as pancr eas, colon, lung, thyroid, bladder and several types of leukemia. Prenylati on of Ras proteins plays a major role in cell proliferation of both normal and cancerous cells, Normal and oncogenic Ras proteins are posttranslationa lly modified by a farnesyl group that promotes membrane binding. Inhibitors of farnesyl protein transferase (FPTase), the enzyme that catalyzes the pr enylation of Ras proteins, inhibit growth of tumor cells. In an effort to i dentify structurally diverse and unique inhibitors of FPTase, a program dev oted to screening of natural products was initiated. This effort led to the identification of 10 different families of compounds, all of which selecti vely inhibit FPTase with a variety of mechanisms that are reviewed in this manuscript. These compounds originated from the fermentations of a number o f microorganisms, either actinomycetes or fungi, isolated from different su bstrates collected in tropical and temperate areas. A chemotaxonomic discus sion on the distribution of each compound among single or different types o f microorganisms, either phylogenetically related or unrelated species, is included.