Navigation Links
Using evolution, UW team creates a template for many new therapeutic agents
Date:9/9/2007

MADISON - By guiding an enzyme down a new evolutionary pathway, a team of University of Wisconsin-Madison researchers has created a new form of an enzyme capable of producing a range of potential new therapeutic agents with anticancer and antibiotic properties.

Writing in the current issue (Sept. 9, 2007) of the journal Nature Chemical Biology, a team of researchers from the UW-Madison School of Pharmacy describes a novel enzyme capable of changing the chemical properties of a variety of existing drugs and small molecules to make new agents to treat cancer and fight infection.

"We're finding this enzyme glycosylates all sorts of molecules," says Jon Thorson, a UW-Madison professor of pharmaceutical sciences describing the process of adding natural sugar molecules to other chemical molecules to enhance their biological effects.

The newly evolved enzyme developed by Thorson and colleagues Gavin. J. Williams and Changsheng Zhang, according to Thorson, is akin to a "Swiss Army enzyme," a catalyst that can decorate many different chemical molecules with all sorts of sugars to alter their biological effects.

Enzymes are proteins that act as catalysts across biology, from single-celled organisms to humans. They promote chemical reactions in cells and are used widely in industry for everything from making beer and cheese to producing paper and biofuel.

They are also important for making so-called natural drugs, therapeutic agents based on the blueprints of chemicals produced in nature by plants and microorganisms. Such natural sugar-bearing chemicals are the basis for some of medicine's most potent antibiotics and anticancer drugs as exemplified by the antibiotic erythromycin and the anticancer drug doxorubicin.

Important chemical features of such drugs are natural sugars, molecules that often determine a chemical compound's biological effects. Although scientists can sometimes manipulate how sugars are added or subtracted to a chemical molecule to alter its therapeutic properties, it is difficult and not always possible to routinely modify them to enhance their beneficial effects.

The new enzyme was created by generating random mutations in genes that make a naturally occurring enzyme. The altered genes were then put into a bacterium, which fabricated a series of randomly mutated new enzymes. These enzyme variants were then tested in a high throughput screen where chemical molecules engineered to fluoresce stop glowing when a sugar is successfully attached.

"We're transferring the sugar to a beacon," Thorson explains. "When you attach a sugar, you shut off the fluorescence."

The development of the screen, according to Thorson, was critical, overcoming a key limitation in the glycosyltransferase field.

"We're assaying hundreds of very interesting drug-like molecules now with newly evolved glycosyltransferases. The ability to rapidly evolve these enzymes has opened a lot of doors."

The range of potential therapeutic agents that might be generated with the new technology includes important anti-inflammatory and anti-cancer compounds, and antibiotics.

What's more, the work could lead to the creation of a "super bug," an engineered bacterium that can perform the entire process in a laboratory dish: "There's no doubt that this is going to work in vivo," says Thorson. "We can create a bug where you feed it sugars and the compounds you want to hang those sugars on" to arrive at new medicines.


'/>"/>

Contact: Jon Thorson
jsthorson@pharmacy.wisc.edu
608-262-3829
University of Wisconsin-Madison
Source:Eurekalert

Related biology news :

1. University of Manchester makes made-to-measure skin and bones a reality using inkjet printers
2. Purdue proves concept of using nano-materials for drug discovery
3. An entropy-based gene selection method for cancer classification using microarray data
4. Newly Discovered Compound Blocks Known Cancer-Causing Protein
5. Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer
6. New methods of gene delivery using lasers
7. Rush Physicians Using Gene Therapy For Heart Patients With Moderate To Severe Chest Pains Who Do Not Benefit From Other Treatments
8. Doctors closer to using gene analysis to help trauma patients
9. PHACCS, an online tool for estimating the structure and diversity of uncultured viral communities using metagenomic information
10. Researchers pioneer new gene therapy technique using natural repair process
11. Researchers Closer To Helping Hearing-Impaired Using Stem Cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/7/2016)... , Dec. 7, 2016   Avanade ... successful Formula One teams in history, exploit biometric data ... stop performance and maintain the competitive edge against their ... 2016. Avanade has worked with Williams ... range of biometric data (heart rate, breathing rate, temperature ...
(Date:12/5/2016)... WASHINGTON , Dec. 5, 2016  The ... (NIJ), today published "Can CT Scans Enhance or ... examines the potential of supporting or replacing forensic ... a CT scan. In response to ... NIJ is exploring using CT scans as a ...
(Date:11/29/2016)... -- BioDirection, a privately held medical device company developing ... of concussion and other traumatic brain injury (TBI), announced ... with the U.S. Food and Drug Administration (FDA) to ... the meeting company representatives reviewed plans for clinical development ... of a planned pilot trial. "We ...
Breaking Biology News(10 mins):
(Date:12/8/2016)... SAN DIEGO , Dec. 8, 2016 /PRNewswire/ ... presented demonstrating the role of the Breast Cancer ... stage, ER+ breast cancer are most at-risk for ... therapy. Data include results from three studies advancing ... provide information related to tumor biology and inform ...
(Date:12/8/2016)... 8, 2016 Oxford ... erweitert seine Palette an anpassbaren SureSeq™ NGS-Panels mit ... Panels, das ein schnelles und kostengünstiges Studium der ... bietet eine Erkennung von Einzel-Nukleotid-Variationen (Single Nucleotide Variation, ... einzigen kleinen Panel und ermöglicht eine individuelle Anpassung ...
(Date:12/8/2016)... CA (PRWEB) , ... December 08, 2016 , ... ... as finalists in the World Technology Awards. uBiome is one of just six ... across all categories. , In addition to uBiome, companies nominated as finalists in ...
(Date:12/8/2016)... Dec. 8, 2016 Savannah River Remediation ... and selected NewTechBio,s NT-MAX Lake & Pond ... beneficial bacteria, in conjunction with Hexa Armor/ Rhombo ... with National Pollutant Discharge Elimination System requirements. ... a steady history of elevated pH levels, above ...
Breaking Biology Technology: