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Biochemistry & Biophysics
New Approach to Thyroid Surgery Eliminates Neck Scar PDF Print E-mail
Friday, 19 August 2011 00:57
As the rate of thyroid cancer continues to climb, doctors are urging patients to be more cautious about thyroid nodules, a common disorder that is responsible for a small but growing number of thyroid cancer cases. Thyroid nodules affect nearly 13 million Americans and are a result of abnormal cell growth on the gland.
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Mimicking Biological Complexity, in a Tiny Particle PDF Print E-mail
Friday, 19 August 2011 00:00
Tiny particles made of polymers hold great promise for targeted delivery of drugs and as structural scaffolds for building artificial tissues. However, current production methods for such microparticles yield a limited array of shapes and can only be made with certain materials, restricting their usefulness.
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E. Coli, Salmonella May Lurk in Unwashable Places in Produce PDF Print E-mail
Wednesday, 17 August 2011 00:58
Sanitizing the outside of produce may not be enough to remove harmful food pathogens, according to a Purdue University study that demonstrated that Salmonella and E. coli can live inside plant tissues.
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Scientists Have New Help Finding Their Way Around Brain's Nooks and Crannies PDF Print E-mail
Wednesday, 17 August 2011 00:54
Like explorers mapping a new planet, scientists probing the brain need every type of landmark they can get. Each mountain, river or forest helps scientists find their way through the intricacies of the human brain.
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Radiofrequency Ablation Safely and Effectively Treats Barrett's Esophagus, Study Suggests PDF Print E-mail
Monday, 15 August 2011 00:21
Radiofrequency ablation (RFA) is a safe and effective option for the treatment of dysplastic Barrett's esophagus that attains lasting response, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association.
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Baker's Yeast Protects Against Fatal Infections PDF Print E-mail
Friday, 12 August 2011 00:52
Injecting mice with simple baker's yeast protects against the fatal fungal infection, aspergillosis, according to research published in the Journal of Medical Microbiology. The work could lead to the development of a human vaccine that protects immunocompromised people against a range of life-threatening fungal infections, for which current therapy often fails.
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Engineers Reverse E. Coli Metabolism for Quick Production of Fuels, Chemicals PDF Print E-mail
Friday, 12 August 2011 00:48
In a biotechnological tour de force, Rice University engineering researchers this week unveiled a new method for rapidly converting simple glucose into biofuels and petrochemical substitutes. In a paper published online in Nature, Rice's team described how it reversed one of the most efficient of all metabolic pathways -- the beta oxidation cycle -- to engineer bacteria that produce biofuel at a breakneck pace.
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Stress Protection: How Blue-Green Algae Hoard Energy PDF Print E-mail
Wednesday, 10 August 2011 00:02
Under normal conditions, cyanobacteria, also termed blue-green algae, build up energy reserves that allow them to survive under stress such as long periods of darkness. They do this by means of a molecular switch in an enzyme. By removing this switch, researchers now show that it is possible to use the excess energy of the bacteria for biotechnological purposes such as hydrogen production, without the bacteria suffering.
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Finding About Cell Division and Metabolism May Provide Insight Into Neurodegenerative Disorders PDF Print E-mail
Monday, 08 August 2011 16:00
Cells are the building blocks of the human body. They are a focus of scientific study, because when things go wrong at the cellular and molecular level the consequences for human health are often significant.
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New Conducting Properties Discovered in Bacteria-Produced Wires PDF Print E-mail
Monday, 08 August 2011 00:55
The discovery of a fundamental, previously unknown property of microbial nanowires in the bacterium Geobacter sulfurreducens that allows electron transport across long distances could revolutionize nanotechnology and bioelectronics, says a team of physicists and microbiologists at the University of Massachusetts Amherst.
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Research Team Achieves First 2-Color STED Microscopy of Living Cells PDF Print E-mail
Friday, 19 August 2011 00:02
Researchers are able to achieve extremely high-resolution microscopy through a process known as stimulated emission depletion (STED) microscopy. This cutting-edge imaging system has pushed the performance of microscopes significantly past the classical limit, enabling them to image features that are even smaller than the wavelength of light used to study them.
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Overcoming Antibiotic Resistance PDF Print E-mail
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Thursday, 18 August 2011 22:58

 

To get to the modified antibiotic from the natural product (shown), replace the disaccharide (black) with hydrogen to form the aglycone and replace the oxygen in a key amide (red) with nitrogen to form an amidine.
To get to the modified antibiotic from the natural product (shown), replace the disaccharide (black) with hydrogen to form the aglycone and replace the oxygen in a key amide (red) with nitrogen to form an amidine.

 

 

 

 

 

 

 

 

Researchers have achieved a key step toward a long-sought goal: redesigning the antibiotic vancomycin so that it kills some bacteria that have become resistant to it. The work could  lead to drugs effective against difficult-to-treat infections.

Discovered by Eli Lilly & Co. researchers in the 1950s, vancomycin is a glycosylated natural product that has become the antibiotic of last resort for hard-to-treat infections, such as those caused by antibiotic-resistant staphylococcal and enterococcal bacteria.

But eventually bacteria developed resistance to vancomycin, too, in some cases by changing an amide to an ester in a glycopeptide cell-wall precursor. Antibiotic mechanisms expert Christopher A. Walsh of Harvard Medical School and coworkers showed that the modified glycopeptide is less likely to  interact with one of vancomycin’s oxygens, thereby inhibiting  binding of the drug to the glycopeptide and  turning off the drug’s antibiotic action.

Now, synthetic chemist Dale L. Boger and coworkers at Scripps Research Institute, in La Jolla, Calif., have turned the tables on these resistant bacteria by synthesizing a form of vancomycin in which an amide containing the interacting oxygen has been changed to an amidine, which lacks oxygen (J. Am. Chem. Soc., DOI:10.1021/ja207142h). Other researchers had proposed that such a modification could restore vancomycin’s efficacy against resistant bacteria, but Boger’s is the first group to create the modified vancomycin, which is difficult to synthesize.

The researchers simplified the challenge by modifying only vancomycin’s aglycon, which is vancomycin minus its disaccharide group. In in vitro tests, the amidinated aglycon achieves about the same level of activity as vancomycin against antibiotic-sensitive bacteria and retains a similar level of activity against bacteria with the resistant amide-to-ester modification, making it about 1,000 times stronger than the parent compound against those microorganisms.

For the amidinated aglycon to be effective in vivo, however, the disaccharide or a modified version of it would have to be installed, and this would make synthesis of the redesigned vancomycin yet more difficult.

Synthesis of the amidinated aglycon “is a highly creative and rationally targeted approach” to combatting bacterial drug resistance, says antibiotic-resistance specialist Gerry Wright of McMaster University, Hamilton, Ontario, Canada. The big challenge will be to figure out if this can be applied in real-life drug discovery efforts.”

The new study “is the culmination of a monumental effort by Boger and his group to resuscitate this antibiotic scaffold against vancomycin-resistant enterococci,” Walsh comments. It “shows medicinal chemistry mastery in this forbiddingly complex scaffold. It does open the question of whether anyone could make” a fully glycosylated amidinated vancomycin analog “on a practical scale,” but one cannot rule that out, he says.

Chemical & Engineering News
ISSN 0009-2347
Copyright © 2011 American Chemical Society

Overcoming Antibiotic Resistance

Medicinal Chemistry: Modified vancomycin shows promise against hard-to-treat bacteria

Stu Borman

To get to the modified antibiotic from the natural product (shown), replace the disaccharide (black) with hydrogen to form the aglycone and replace the oxygen in a key amide (red) with nitrogen to form an amidine.
 To get to the modified antibiotic from the natural product (shown), replace the disaccharide (black) with hydrogen to form the aglycone and replace the oxygen in a key amide (red) with nitrogen to form an amidine.
 
How Fatty Diets Cause Diabetes PDF Print E-mail
Wednesday, 17 August 2011 00:56
Newly diagnosed type 2 diabetics tend to have one thing in common: obesity. Exactly how diet and obesity trigger diabetes has long been the subject of intense scientific research. A new study led by Jamey D. Marth, Ph.D., director of the Center for Nanomedicine, a collaboration between the University of California, Santa Barbara and Sanford-Burnham Medical Research Institute (Sanford-Burnham), has revealed a pathway that links high-fat diets to a sequence of molecular events responsible for the onset and severity of diabetes.
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Route for Eliciting HIV-Neutralizing Antibodies Mapped PDF Print E-mail
Monday, 15 August 2011 00:23
Researchers have traced in detail how certain powerful HIV neutralizing antibodies evolve, a finding that generates vital clues to guide the design of a preventive HIV vaccine, according to a study appearing in Science Express this week.
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Most Common Bladder Cancer Tumor Sequenced PDF Print E-mail
Monday, 15 August 2011 00:19
In an article published online this week in Nature Genetics, a University of Colorado Cancer Center team in partnership with universities in China and Denmark reports the first genetic sequencing of urothelial (transitional) carcinoma, the most prevalent type of bladder cancer.
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New Insights Into the How the Powerhouse of the Cell Works PDF Print E-mail
Friday, 12 August 2011 00:51
Mitochondria are the powerhouse of the cell. They are thought to have evolved more than a billion years ago from primitive bacterium which was engulfed by an early eukaryotic cell resulting in endosymbiotic relationships between the host cell and the newly formed organelle.
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Cell-Based Alternative to Animal Testing? Genomic Biomarker Signature Can Predict Skin Sensitizers, Study Finds PDF Print E-mail
Wednesday, 10 August 2011 00:59
European legislation restricts animal testing within the pharmaceutical and cosmetic industries and companies are increasingly looking at alternative systems to ensure that their products are safe to use.
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Researchers Use Neutrons to Spy On the Elusive Hydronium Ion: Unprecedented Proof of Ion's Role in Enzymatic Process PDF Print E-mail
Wednesday, 10 August 2011 00:00
A Los Alamos National Laboratory research team has harnessed neutrons to view for the first time the critical role that an elusive molecule plays in certain biological reactions. The effort could aid in treatment of peptic ulcers or acid reflux disease, or allow for more efficient conversion of woody waste into transportation fuels.
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How Yeast Chromosomes Avoid the Bad Breaks PDF Print E-mail
Monday, 08 August 2011 15:59
The human genome is peppered with repeated DNA elements that can vary from a few to thousands of consecutive copies of the same sequence. During meiosis -- the cell division that produces sperm and eggs -- repetitive elements place the genome at risk for dangerous rearrangements from genome reshuffling.
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New Study Identifies Emergence of Multidrug-Resistant Strain of Salmonella PDF Print E-mail
Friday, 05 August 2011 00:36
A new study has identified the recent emergence of a multidrug-resistant strain of Salmonella that has a high level resistance to ciprofloxacin, a common treatment for severe Salmonella infections. The study, led by François-Xavier Weill, MD, and Simon Le Hello, PharmD, at the Pasteur Institute in France, is published in The Journal of Infectious Diseases and is now available online.
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