Chemistry – Page 9

10.10.2012

nobel prize in chemistry

The Nobel Prize in Chemistry was awarded to two Americans today for their work with G Protein Coupled Receptors. G-Protein Coupled receptors are ubiquitous in biological systems and are responsible for sending the signals that help us detect changes in our environment. They are especially important in neurotransmission and hormone signaling pathways. Also, half of known pharmaceutical targets are G-Protein coupled receptors. From the Nobel press release:

Your body is a fine-tuned system of interactions between billions of cells. Each cell has tiny receptors that enable it to sense its environment, so it can adapt to new situtations. Robert Lefkowitz and Brian Kobilka are awarded the 2012 Nobel Prize in Chemistry for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein–coupled receptors.

For a long time, it remained a mystery how cells could sense their environment. Scientists knew that hormones such as adrenalin had powerful effects: increasing blood pressure and making the heart beat faster. They suspected that cell surfaces contained some kind of recipient for hormones. But what these receptors actually consisted of and how they worked remained obscured for most of the 20th Century.

Lefkowitz started to use radioactivity in 1968 in order to trace cells’ receptors. He attached an iodine isotope to various hormones, and thanks to the radiation, he managed to unveil several receptors, among those a receptor for adrenalin: β-adrenergic receptor. His team of researchers extracted the receptor from its hiding place in the cell wall and gained an initial understanding of how it works.

The team achieved its next big step during the 1980s. The newly recruited Kobilka accepted the challenge to isolate the gene that codes for the β-adrenergic receptor from the gigantic human genome. His creative approach allowed him to attain his goal. When the researchers analyzed the gene, they discovered that the receptor was similar to one in the eye that captures light. They realized that there is a whole family of receptors that look alike and function in the same manner.

Today this family is referred to as G-protein–coupled receptors. About a thousand genes code for such receptors, for example, for light, flavour, odour, adrenalin, histamine, dopamine and serotonin. About half of all medications achieve their effect through G-protein–coupled receptors.

Also, check out the New York Times.

10.06.2012

“awesome” synthesis

Scientists have made amazing progress in the synthesis of biologics

Scientists have created a way to add a uniform coating of sugars to the protein erythropoietin. Erythropoietin is a protein that induces production of red blood cells. In the body, the sugars coating the surface of the protein are essential to its function. Samuel Danishefsky, who is a synthetic chemist at Sloan Kettering, has developed a synthesis of the protein which has smaller sugar chains, but still allow the protein to carry out its function. From Science:

Last week, the MSKCC-Columbia team reported online in Angewandte Chemie that for the first time they had synthesized EPO with a uniform coating of sugar chains that decorate the outside of the natural molecule. EPO is a hormone produced by the kidneys that stimulates the production of red blood cells. It’s also administered as a drug, sometimes called a biologic, to anemia patients, as well as those with cancer who have undergone radiation and chemotherapy treatments that can damage red blood cells.

“EPO is the most complex biologic synthesized to date,” says Laura Kiessling, a chemist at the University of Wisconsin, Madison, who calls the accomplishment “remarkable.” Peng George Wang, a synthetic chemist at Georgia State University in Atlanta, agrees that the new synthetic ascent is “an awesome achievement,” because the researchers not only synthesized a complex protein but also decorated it with a uniform set of sugars—a feat that has long been out of reach. A decade ago, “we could not imagine it could be a target. It was just too complicated,” Wang says. Danishefsky notes that the feat rests on a decade of advances in fabricating portions of the protein, linking them together, and then coming up with novel chemical techniques to tie sugar chains on at precise locations. Although the version of EPO the group made has shorter sugar chains than those typically found in organisms, biochemical studies showed that it carried out the same function of stimulating the production of red blood cells.

10.04.2012

arsenate or phosphate controversy put to bed

Arsenate

A while back some scientists thought they had discovered a bacteria that could thrive on arsenic. They hypothesized that arsenic was being incorporated into the organism’s molecules in place of phosphorus without any problem. This was later discovered to be incorrect. A paper in Nature Magazine details how bacteria discriminate between arsenic and phosphorus. From Scientific American:

“This work provides in a sense an answer to how GFAJ-1 (and related bacteria) can thrive in very high arsenic concentrations,” say Tobias Erb and Julia Vorholt of the Swiss Federal Institute of Technology in Zurich, co-authors of the latest paper, who were also co-authors on a follow-up paper that cast doubt on the initial arsenic-life claims.

The researchers looked at five types of phosphate-binding protein — which bind phosphate in a molecular pathway that brings it into the cells — from four species of bacteria. Two of the bacterial species were sensitive to arsenate and two were resistant to it. To test how effective these proteins were at discriminating between phosphate and arsenate, the researchers put them in solution with a set amount of phosphate and different concentrations of arsenate for 24 hours, and then checked which of the molecules the proteins would bind to.

Their threshold for when ‘discrimination’ broke down was when 50% of the proteins ended up bound to arsenate — indicating that the ability to discriminate had been overwhelmed. Even in solutions containing 500-fold more arsenate than phosphate, all five proteins were still able to preferentially bind phosphate. And one protein, from the Mono Lake bacterium, could do so at arsenate excesses of up to 4,500-fold over phosphate.

The paper includes detailed structures of both phosphate and arsenate bound to bacterial protein. You can see how the arsenate’s larger size impedes protein binding. Please check out the source link for more.

GOLLYGEE!

Category: Chemistry (page 9 of 15)

nobel prize in chemistry

“awesome” synthesis

arsenate or phosphate controversy put to bed