3-D Turing pattern formation in a chemical reaction system

In a report in this week’s issue of Science, Brandeis professor Irving Epstein, senior research associate Vladimir Vanag and postdoc Tamas Bansagi use tomographic methods, like those employed in a medical CAT scan, but using visible light in this case, to obtain the first three-dimensional images of Turing patterns. These patterns have been proposed as a mechanism for morphogenesis in living systems, perhaps offering an explanation for phenomena like “how the leopard gets its spots” or skeletal structure in developing limbs. .

Commentary: Wired Science

New route to lycopodium alkaloids

The lycopodium alkaloids are a large and extensively studied alkaloid family. Huperzine A (1), the medicinally most significant lycopodine alkaloid as a potential treatment for Alzheimer’s disease, functions as an acetylcholinesterase inhibitor but may have other roles as has been addressed in several recent reviews.  Sauroine (2, 7,8-dihydroxylycopodine), from Huperzia saururus, was reported in 2004 and shown in 2009 to improve memory retention in the step-down test in male Wistar rats, significantly increasing hippocampal plasticity. 7-Hydroxylycopodine (3), from Huperzia serrata, was also reported in 2004 and may have related biological activity.

In their recent Organic Letters paper entitled the Synthesis of (±)-7-Hydroxylycopodine, the Snider lab at Brandeis developed a new general route to these bridgehead hydroxylated lycopodines. They reported a practical six-step synthesis of 7-hydroxylycopodine which makes it readily available for further biological evaluation. The key step of the synthesis is the treatment of bicyclic enol ether 4 with 60% sulfuric acid that affords tricyclic amino alcohol 5, which is further elaborated to 7-hydroxylycopodine (3) in three steps. The application of this route to the synthesis of sauroine (2) is now under investigation.

HHMI Professors on changing the culture of science education

13 HHMI Professors, including Brandeis’s Irving Epstein, wrote a recent editorial in the journal Science calling for a reexamination of priorities between research and teaching at research universities. The seven initiatives they call for:

  1. Educate faculty about research on learning.
  2. Create awards and named professorships that provide research support for outstanding teachers.
  3. Require excellence in teaching for promotion.
  4. Create teaching discussion groups.
  5. Create cross-disciplinary programs in college-level learning.
  6. Provide ongoing support for effective science teaching.
  7. Engage chairs, deans, and presidents.

Strong stuff — will we respond to this challenge?

Phantasmidine, a Nicotinic Receptor Agonist from Ecuadoran Poison Frogs

IIn 1992, the lab of the late John Daly at NIH reported the isolation of epibatidine (1) from the skin of an Ecuadorian poison frog.  In addition to being a toxin, epibatidine has potent analgesic activity. Subsequent studies showed that this activity resulted from interaction with acetylcholine nicotinic receptors (nAChRs) with binding to some of the receptors at sub nanomolar levels.  The binding to several different types of nAChRs may be responsible for its non-selective activity.

In 2010, the Daly group reported the isolation and tentative structure determination of the epibatidine congener phantasmidine (2) from a total sample of only 20 micrograms. Preliminary biological studies with the limited material available indicated that phantasmidine (2) differs from epibatidine (1) by being selective for β4-containing nicotinic receptors, suggesting that phantasmidine might fill a niche for characterization of these receptors. However, the limited natural material available precluded detailed pharmacological analysis and definitive structure determination.

In their recent paper in Organic Letters entitled the Synthesis of Phantasmidine, the Snider lab at Brandeis reported a short and efficient synthesis of phantasmidine that confirmed the tentative structure and makes ample material readily available for further biological evaluation, which is currently in progress.  To prepare the tetracyclic framework, they invented a new tandem intramolecular aldol reaction-nucleophilic aromatic substitution reaction to form both five membered rings in a single reaction.   Treatment of keto amide 3 with sodium hydroxide gave aldol adduct 4 which cyclized to lactam 5.  Reduction of the lactam completed a practical synthesis of phantasmidine (2).

Spring-loading the active site of cytochrome P450

Enzymes differ from other catalysts in the exceptional substrate selectivity they exhibit.  However, the active sites of related enzymes are often very similar, even though different substrates are acted upon (for example in the superfamily of cytochrome P450s).  How does a given enzyme preferentially bind a particular substrate?  In a new paper appearing in the jounal Metallomics, Chemistry grad student Marina Dang and Profs. Susan Sondej Pochapsky and Thomas Pochapsky use nuclear magnetic resonance (NMR) to identify a helical structure remote from the active site of the enzyme cytochrome P450cam that is responsive to changes in substrate.  They propose that this helix can adjust the position of residues that contact substrate in the enzyme active site, much like the spring that holds batteries in place against electrical contacts in a flashlight.

Back to class

2010 Beckman Scholar Philip Braunstein ’12 discusses his research project in the Hedstrom lab at the last class meeting of Organic Chemistry CHEM 25a. Training the scholars in communicating science and improving the visibility of undergraduate research are key components of the Beckman Scholars program.

Photographs by Nathaniel Freedman

Protected by Akismet
Blog with WordPress

Welcome Guest | Login (Brandeis Members Only)