Chemistry – Page 7

03.22.2013

a death receptor crystal structure

Illustrations of the binding pockets of 5-HT1B and 5-HT2b Serotonin receptors. Image from Science via C&EN.

Receptors for the neurotransmitter serotonin are popular drug targets. Drugs that target these receptors are used to treat problems like depression and migraine headaches. Serotonin receptors are also the targets of some psychedelic drugs like LSD and mescaline.

There are at least 14 subtypes of serotonin receptors known. Most of the drugs that target one subtype of serotonin receptor will also target the others. This is usually not a problem except in the case of one type called 5-HT2B. This receptor is called the death receptor because activating it can cause heart problems that will lead to death. This receptor is to be avoided.

Chemical & Engineering News brings word of two crystal structures that might help drug developers better avoid activating the 5-HT2B subtype of receptors:

Help will come from new crystal structures of 5-HT_1B and of 5-HT_2B, each bound to the migraine drugs ergotamine and dihydroergotamine (Science,DOI: 10.1126/science.1232807 and DOI: 10.1126/science.1232808). The findings provide a blueprint for designing more selective 5-HT inhibitors.

The team behind the structures includes Raymond C. Stevens, a chemistry and molecular biology professor at Scripps Research Institute, La Jolla, Calif.; Bryan L. Roth, a pharmacology professor at the University of North Carolina; H. Eric Xu, director of the Center for Structural Biology & Drug Discovery at Van Andel Research Institute in Grand Rapids, Mich., and Hualiang Jiang, a professor at the Shanghai Institute of Materia Medica.

This is major news for our field,” adds Kathryn A. Cunningham, a professor in the pharmacology and toxicology department at the University of Texas Medical Branch. “The structures were solved for the receptor-ligand cocrystals, which provides important insights into how the receptors work.”

The importance of selectivity was most infamously illustrated in the 1990s by the obesity treatment Fen-Phen (fenfluramine-phentermine). Both molecules targeted 5-HT receptors, but they weren’t selective enough. Unbeknown to scientists, they also bound to the death receptor, 5-HT2B, triggering sometimes-fatal cardiovascular side-effects. Fen-Phen’s withdrawal from the market was the largest in history and cost its manufacturer, Wyeth, billions of dollars in damages.

Check out the original research here and here.

02.25.2013

america’s impending helium shortage

In this week’s Science Magazine, Adrian Cho brings word of a looming shortage of helium in America:

For the second time in 8 months, a bill has been introduced in Congress that would prevent an acute but wholly self-inflicted shortage of helium from striking later this year. The shortage would hamstring research in a variety of fields. “Unless Congress takes swift action, the U.S. will float off the helium cliff,” said Representative Doc Hastings (R–WA), chair of the House of Representatives Natural Resources Committee and co-sponsor of the bipartisan bill, during a hearing this week.

Here’s the problem. Since 1996, the U.S. government has been selling off its vast reserve of helium, a legacy of the Cold War, which is held in an underground reservoir near Amarillo, Texas. Those sales supply 42% of the crude helium consumed in the United States and 35% of the crude helium consumed globally. But by law, they will continue only until the Bureau of Land Management (BLM), which controls the reserve, recoups the $1.4 billion cost of developing the reserve. BLM will reach that break-even point by the end of this fiscal year, 30 September. At that point, BLM will have no authority to sell the remaining helium unless Congress acts.

More here.

02.20.2013

water on the moon

Image from the first moon walk

From Popular Science:

Scientists have known for almost five years now that the moon is watery–or at least that lots of water molecules are trapped in its crust and its permanently dark, frozen craters. The prevailing theory is that this water comes from molecules in the solar system. But maybe the moon has had water all along, according to a new study of Apollo moon rocks.

Hejiu Hui of Notre Dame, Youxue Zhang of the University of Michigan and their colleagues studied several rocks from the lunar highlands, recovered during the late Apollo missions. One rock was nicknamed the “genesis rock” after Apollo 15 astronauts recovered it on a crater rim. The rock was thought to have come from the moon’s primordial crust.

The researchers used infrared spectroscopy to peer inside the rocks without disturbing them, and were able to analyze the rocks’ water content. It’s not really water, per se, but the related chemical known as hydroxyl, which contains one atom each of oxygen and hydrogen.

GOLLYGEE!

Category: Chemistry (page 7 of 15)

a death receptor crystal structure

america’s impending helium shortage

water on the moon