Topic
Macbecin
About: Macbecin is a research topic. Over the lifetime, 15 publications have been published within this topic receiving 886 citations. The topic is also known as: macbecin.
Papers
TL;DR: The results suggest that benzoquinonoid ansamycins have no direct effect on src kinase but destroy its intracellular environment, resulting in an irreversible alteration of p60src and loss of catalytic activity.
Abstract: Three benzenoid ansamycin antibiotics (herbimycin, macbecin, and geldanamycin) were found to reduce the intracellular phosphorylation of p60src at a permissive temperature (33 degrees C) in a rat kidney cell line infected with a temperature-sensitive mutant of Rous sarcoma virus. This effect was accompanied by morphological changes from the transformed to the normal phenotype. The filamentous staining pattern of actin fibers was observed in the cells treated with these antibiotics at 33 degrees C. Removal of the antibiotics allowed the cells to revert to the transformed morphology. Ansamitocin, another benzenoid ansamycin, and naphthalenoid ansamycins such as streptovaricin and rifamycins did not show this effect. Pulse-labeling of the antibiotic-treated cultures with 32Pi showed a marked reduction of 32P radioactivity incorporated into p60src. A parallel experiment with [35S]methionine showed that synthesis of p60src was slightly inhibited. The immune complex prepared by mixing the herbimycin-treated cell extracts with antibody against p60src was inactive in vitro in phosphorylating the complex itself. On the contrary, the immune complex derived from untreated cells was active in vitro even in the presence of the antibiotics. These results suggest that benzoquinonoid ansamycins have no direct effect on src kinase but destroy its intracellular environment, resulting in an irreversible alteration of p60src and loss of catalytic activity.
244 citations
TL;DR: In this article, a convergent asymmetric synthesis of the antitumor antibiotic macbecin I has been achieved, where six of the seven stereogenic centers within the target structure were controlled using asymmetric aldol methodology, while the final stereogenic center was established through internal asymmetric induction.
Abstract: A convergent asymmetric synthesis of the antitumor antibiotic macbecin I has been achieved. Six of the seven stereogenic centers within the target structure were controlled using asymmetric aldol methodology, while the final stereogenic center was established through internal asymmetric induction. Fragment coupling was accomplished using a mild, titanium tetrachloride mediated aldol reaction. The C 1 -C 5 unsaturated dienic ester was stereoselectively incorporated through a kinetically controlled Horner-Emmons olefination. Macrolactamization and subsequent refunctionalization afforded macbecin I
82 citations
TL;DR: The protein chaperone Hsp90 and its co-chaperone Sba1/p23 are found to accumulate in the nucleus of haploid yeast cells as glucose is exhausted and in sporulating diploids.
Abstract: The 90-kDa heat-shock protein (Hsp90) operates in the context of a multichaperone complex to promote maturation of nuclear and cytoplasmic clients. We have discovered that Hsp90 and the cochaperone Sba1/p23 accumulate in the nucleus of quiescent Saccharomyces cerevisiae cells. Hsp90 nuclear accumulation was unaffected in sba1Delta cells, demonstrating that Hsp82 translocates independently of Sba1. Translocation of both chaperones was dependent on the alpha/beta importin SRP1/KAP95. Hsp90 nuclear retention was coincident with glucose exhaustion and seems to be a starvation-specific response, as heat shock or 10% ethanol stress failed to elicit translocation. We generated nuclear accumulation-defective HSP82 mutants to probe the nature of this targeting event and identified a mutant with a single amino acid substitution (I578F) sufficient to retain Hsp90 in the cytoplasm in quiescent cells. Diploid hsp82-I578F cells exhibited pronounced defects in spore wall construction and maturation, resulting in catastrophic sporulation. The mislocalization and sporulation phenotypes were shared by another previously identified HSP82 mutant allele. Pharmacological inhibition of Hsp90 with macbecin in sporulating diploid cells also blocked spore formation, underscoring the importance of this chaperone in this developmental program.
47 citations
TL;DR: Exposure to low-temperature augments the α(2C)-AR transport to the plasma membrane by releasing the inhibitory activity of HSP90 on the receptor traffic, findings which may have clinical relevance for the diagnostic and treatment of Raynaud Phenomenon.
29 citations
TL;DR: Diol 4.Diol comprising the C11-C21 ansa subunit of the antitumor antibiotic macbecin I has been prepared by a sequence incorporating sequential Wittig rearrangements to establish the carbon skeleton and remote functionality of the macBecin ansa system.
19 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2017 | 1 |
| 2011 | 1 |
| 2010 | 1 |
| 2008 | 2 |
| 2003 | 1 |
| 1999 | 1 |