JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Rare Streptomyces N-formyl amino-salicylamides inhibit oncogenic K-Ras.
Org. Lett.
PUBLISHED: 09-19-2014
Show Abstract
Hide Abstract
During a search for inhibitors of oncogenic K-Ras, we detected two known and two new examples of the rare neoantimycin structure class from a liquid cultivation of Streptomyces orinoci, and reassigned/assigned structures to all based on detailed spectroscopic analysis and microscale C3 Marfey's and C3 Mosher chemical degradation/derivatization/analysis. SAR investigations inclusive of the biosynthetically related antimycins and respirantin, and synthetic benzoxazolone, documented a unique N-formyl amino-salicylamide pharmacophore as a potent inhibitor of oncogenic K-Ras.
Related JoVE Video
Wollamides: antimycobacterial cyclic hexapeptides from an Australian soil Streptomyces.
Org. Lett.
PUBLISHED: 09-17-2014
Show Abstract
Hide Abstract
A soil Streptomyces nov. sp. (MST-115088) isolated from semiarid terrain near Wollogorang Station, Queensland, returned two known and two new examples of a rare class of cyclic hexapeptide, desotamides A and B (1 and 2) and E and F (3 and 4), respectively, together with two new d-Orn homologues, wollamides A and B (5 and 6). Structures were assigned by detailed spectroscopic and C3 Marfey's analysis. The desotamides/wollamides exhibit growth inhibitory activity against Gram-positive bacteria (IC50 0.6-7 ?M) and are noncytotoxic to mammalian cells (IC50 >30 ?M). The wollamides exhibit antimycobacterial activity (IC50 2.8 and 3.1 ?M), including reduction in the intracellular mycobacterial survival in murine bone marrow-derived macrophages.
Related JoVE Video
Rare Streptomyces sp. polyketides as modulators of K-Ras localisation.
Org. Biomol. Chem.
PUBLISHED: 05-31-2014
Show Abstract
Hide Abstract
Chemical investigations of a soil-derived Streptomyces sp. led to the isolation of five new polyketides, (+)-oxanthromicin, (±)-hemi-oxanthromicins A/B, (±)-spiro-oxanthromicin A and oxanthroquinone, and the known alkaloid staurosporine, and the detection of four new metastable analogues, (±)-spiro-oxanthromicins B1/B2/C1/C2. Among the compounds tested, SAR investigations established that the synthetic oxanthroquinone ethyl ester and 3-O-methyl-oxanthroquinone ethyl ester were optimal at mislocalising oncogenic mutant K-Ras from the plasma membrane of intact Madin-Darby canine kidney (MDCK) cells (IC50 4.6 and 1.2 ?M), while a sub-EC50 dose of (±)-spiro-oxanthromicin A was optimal at potentiating (750%) the K-Ras inhibitory activity of staurosporine (IC50 60 pM). These studies demonstrate that a rare class of Streptomyces polyketide modulates K-Ras plasma membrane localisation, with implications for the future treatment of K-Ras dependent cancers.
Related JoVE Video
Reveromycins revealed: new polyketide spiroketals from Australian marine-derived and terrestrial Streptomyces spp. A case of natural products vs. artifacts.
Org. Biomol. Chem.
PUBLISHED: 12-14-2010
Show Abstract
Hide Abstract
Chemical analysis of fermentation products from two Australian Streptomyces isolates yielded all four known and twelve new examples of the rare reveromycin class of polyketide spiroketals, including hemi-succinates, hemi-fumarates and hemi-furanoates. Reveromycins were identified with the aid of HPLC-DAD-MS and HPLC-DAD-SPE-NMR methodology, and structures were assigned by detailed spectroscopic analysis. The structural and mechanistic requirements for an unprecedented hemi-succinate?:?ketal-succinyl equilibrium were defined and provided a basis for proposing that reveromycin 4-methyl esters and 5,6-spiroketals were artifacts. A plausible reveromycin polyketide biosynthesis is proposed, requiring a 2-methylsuccinyl-CoA starter unit, with flexible incorporation of a C(6-8) polyketide chain extension and diacid esterification units. Structure activity relationship investigations by co-metabolites were used to assess the anticancer, antibacterial and antifungal properties of reveromycins.
Related JoVE Video
Cottoquinazoline A and cotteslosins A and B, metabolites from an Australian marine-derived strain of Aspergillus versicolor.
J. Nat. Prod.
PUBLISHED: 02-28-2009
Show Abstract
Hide Abstract
An Australian marine-derived isolate of Aspergillus versicolor (MST-MF495) yielded the known fungal metabolites sterigmatocystin, violaceol I, violaceol II, diorcinol, (-)-cyclopenol, and viridicatol, along with a new alkaloid, cottoquinazoline A (1), and two new cyclopentapeptides, cotteslosins A (2) and B (3). Structures for 1-3 and the known compounds were determined by spectroscopic analysis. The absolute configurations of 1-3 were addressed by chemical degradation and application of the C(3) Marfeys method. The use of "cellophane raft" high-nutrient media as a device for up-regulating secondary metabolite diversity in marine-derived fungi is discussed. The antibacterial properties displayed by A. versicolor (MST-MF495) were attributed to the phenols violaceol I, violaceol II, and diorcinol, while cotteslosins 2 and 3 were identified as weak cytotoxic agents.
Related JoVE Video
Staurosporines disrupt phosphatidylserine trafficking and mislocalize Ras proteins.
J. Biol. Chem.
Show Abstract
Hide Abstract
Oncogenic mutant Ras is frequently expressed in human cancers, but no anti-Ras drugs have been developed. Since membrane association is essential for Ras biological activity, we developed a high content assay for inhibitors of Ras plasma membrane localization. We discovered that staurosporine and analogs potently inhibit Ras plasma membrane binding by blocking endosomal recycling of phosphatidylserine, resulting in redistribution of phosphatidylserine from plasma membrane to endomembrane. Staurosporines are more active against K-Ras than H-Ras. K-Ras is displaced to endosomes and undergoes proteasomal-independent degradation, whereas H-Ras redistributes to the Golgi and is not degraded. K-Ras nanoclustering on the plasma membrane is also inhibited. Ras mislocalization does not correlate with protein kinase C inhibition or induction of apoptosis. Staurosporines selectively abrogate K-Ras signaling and proliferation of K-Ras-transformed cells. These results identify staurosporines as novel inhibitors of phosphatidylserine trafficking, yield new insights into the role of phosphatidylserine and electrostatics in Ras plasma membrane targeting, and validate a new target for anti-Ras therapeutics.
Related JoVE Video
Design and application of in vivo FRET biosensors to identify protein prenylation and nanoclustering inhibitors.
Chem. Biol.
Show Abstract
Hide Abstract
Protein prenylation is required for membrane anchorage of small GTPases. Correct membrane targeting is essential for their biological activity. Signal output of the prenylated proto-oncogene Ras in addition critically depends on its organization into nanoscale proteolipid assemblies of the plasma membrane, so called nanoclusters. While protein prenylation is an established drug target, only a handful of nanoclustering inhibitors are known, partially due to the lack of appropriate assays to screen for such compounds. Here, we describe three cell-based high-throughput screening amenable Förster resonance energy transfer NANOclustering and Prenylation Sensors (NANOPS) that are specific for Ras, Rho, and Rab proteins. Rab-NANOPS provides the first evidence for nanoclustering of Rab proteins. Using NANOPS in a cell-based chemical screen, we now identify macrotetrolides, known ionophoric antibiotics, as submicromolar disruptors of Ras nanoclustering and MAPK signaling.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.