Navigation Links
Scripps Research scientists develop powerful new methodology for stabilizing proteins

La Jolla, CA, February 2, 2011 Embargoed by the journal Science until February 3, 2011, 2 PM, Eastern time - A team of scientists at The Scripps Research Institute has discovered a new way to stabilize proteins the workhorse biological macromolecules found in all organisms. Proteins serve as the functional basis of many types of biologic drugs used to treat everything from arthritis, anemia, and diabetes to cancer.

As described in the February 4, 2011 edition of the journal Science, when the team attached a specific oligomeric array of sugars called a "glycan" to proteins having a defined structure, the proteins were up to 200 times more stable in the test tube. In the body, this stability may translate into longer half-lives for therapies, possibly lowering the overall cost of treatment for certain protein-based drugs and requiring patients to have fewer injections during a course of treatment.

The work may have major implications for the drug industry because there are a large number of protein-based drugs on the market, more in clinical trials, and many more under development worldwide. Nearly all of these protein-based drugs have glycans attached to them and are therefore called "glycoproteins". Glycoprotein-based drugs can be quite expensive to produce and usually need to be administered intravenously.

One of the challenges in producing these drugs has been increasing their stability, which generally extends their half-life in the bloodstream issues that the new discovery appears to address directly.

"We've now provided engineering guidelines for glycoprotein stability," said Scripps Research Professor Jeffery W. Kelly, who is chair of the Department of Molecular and Experimental Medicine, Lita Annenberg Hazen Professor of Chemistry, and member of The Skaggs Institute for Chemical Biology at Scripps Research. Kelly led the study with Scripps Research Associate Professor Evan Powers and Staff Scientist Sarah R. Hanson, in collaboration with Research Associates Elizabeth K. Culyba, Joshua Price, and colleagues.

In Search of Stability

Making therapeutic proteins more stable by attaching glycans to them is nothing new. Scientists have known for many years that the human body widely modifies proteins in this way after they are made inside cells. By some estimates, as many as a third of all types of proteins in the human body are "glycosylated," the scientific name for the process whereby glycans are attached to proteins. Scientists also know that these modifications can be directly linked to protein stability.

Attaching a glycan to one part of a protein can have a dramatic stabilizing effect, accounting for the difference between it lasting in the bloodstream for a few minutes or a few days. But attaching the same glycan to another part of the same protein can have a distinctly different destabilizing effect, turning it into the microscopic equivalent of a cooked egg unfolded and worthless as a medicine.

Scientists who work on these sorts of drugs often try to stabilize their therapeutic proteins with glycans, but until now nobody understood the rules that govern the process nobody even knew for sure if there were general rules governing it. Researchers have always made such modifications through trial-and-error more of a time-consuming art than an exact science.

But now, predicts Powers, "Having a rational design approach will streamline protein drug optimization quite a bit."

Simple Engineering Rules

The new research shows simple engineering rules do exist for achieving stability of glycoproteins in the test tube. In the new paper, the Scripps Research team showed that scientists could dramatically stabilize proteins by integrating the standard N-glycan into a particular part of the protein a structure known as a "reverse turn" containing a certain combination of amino acids. Reverse turns are found in the vast majority of proteins, making this methodology broadly applicable.

The scientists tested their ability to increase the stability of proteins by creating glycoproteins from proteins that are not normally glycosylated leading to increased stabilization in the test tube. These scientists have not yet looked at how long the proteins survive in the bloodstream that work is currently under way. But the team is confident that the principles they discovered will now give scientists a new way to predictably stabilize proteins by design.

Kelly added that this portable stabilizing structural module called the "enhanced aromatic sequon" also leads to more efficient production of glycoproteins by cells, a result that is potentially very important, since glycoproteins remain difficult to produce and purify.


Contact: Mika Ono
Scripps Research Institute

Related medicine news :

1. Scripps Research scientists find measles natural nemesis
2. Scripps Research scientists awarded $2.35 million to study new obesity treatment
3. Scripps Research scientists identify first synthetic activator of 2 critical proteins
4. Scripps Clinic nurse to receive 2010 ASTRO Nurse Excellence Award
5. Scripps and Trius team up to develop new antibiotics with US Department of Defense grant
6. Scripps Research scientists solve long-standing mystery of protein quality control mechanism
7. NIH awards Scripps Florida scientists $2.3 Million to develop drug addiction treatments
8. Scripps Research scientists uncover previously unknown natural mechanism that controls cocaine use
9. Scripps Center for Executive Health Now Offers Genetic Testing
10. Scripps Research scientists share $2 million in Florida state research grants
11. Scripps Announces Plans for Region's First Proton Therapy Center; $185 Million Facility to Offer Advanced Care to Cancer Patients
Post Your Comments:
(Date:11/30/2015)... ... November 30, 2015 , ... 1Heart Caregiver ... of the Federation of Philippine American Chambers of Commerce held from November 6-8, ... , 1Heart Caregiver Services, as an active delegate from the Philippine American Chamber ...
(Date:11/30/2015)... , ... November 30, 2015 , ... Until now, the ... set forth in the MOMS (Management of Myelomeningocele Study) trial. One of these exclusion ... and Prevention), a BMI of 18.5 to 24.9 is considered normal, 25 - 29.9 ...
(Date:11/30/2015)... ... ... According to research by the National Association of Dental ... certified or obtain continuing education. To increase awareness of the lack of standards ... inform dentists that the technicians they trust could lack the skills and knowledge ...
(Date:11/30/2015)... Fla. (PRWEB) , ... November 30, 2015 , ... MOSI ... Land, and Sea along with Back to the Jurassic to their collection of interactive ... INDE has created dynamic worlds that will allow guests to get closer than ever ...
(Date:11/30/2015)... ... November 30, 2015 , ... In ... Halloween festivities, the Word of Life Christian Church of Flint, MI, hosted a ... a giant 1.25 ton pile of candy dubbed “Candy Mountain”. , A Forever ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... SAN DIEGO , Nov. 30, 2015 ... ARNA ) today announced that the U.S. Food ... New Drug Application (NDA) for an extended release formulation ... offer patients a chronic weight management treatment in a ... currently approved as an adjunct to a reduced-calorie diet ...
(Date:11/30/2015)... MOUNTLAKE TERRACE, Wash. and ST. ... Cross and Express Scripts (NASDAQ: ESRX ) today ... benefit agreement. The partnership, which began in 1999, will ... --> --> After evaluating pharmacy ... process, Premera concluded that Express Scripts continues to offer ...
(Date:11/30/2015)... N.H. , Nov. 30, 2015 ... that it will feature its latest solutions for ... early identification of cancer at the Radiological Society ... Chicago from November 29 ... recent product advances including iReveal®, an automated breast ...
Breaking Medicine Technology: