Navigation Links
Purifying proteins: Rensselaer researchers use NMR to improve drug development
Date:9/29/2010

Troy, N.Y. The purification of drug components is a large hurdle facing modern drug development. This is particularly true of drugs that utilize proteins, which are notoriously difficult to separate from other potentially deadly impurities. Scientists within the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer Polytechnic Institute are using nuclear magnetic resonance (NMR) to understand and improve an important protein purification process.

"We hope to use our insights to help those in the industry develop improved processes to provide much less expensive drugs and dramatically reduce healthcare costs," said paper author and William Weightman Walker Professor of Polymer Engineering Steven Cramer of Rensselaer.

His team's findings are published in the Sept. 2 online early edition of the journal Proceedings of the National Academy of Sciences (PNAS ) in a paper titled "Evaluation of protein absorption and preferred binding regions in multimodal chromatography using NMR." The research was funded by the National Science Foundation (NSF).

The process of multimodal chromatography has recently generated significant interest in the pharmaceutical industry. At its most basic, this process separates proteins from their surrounding materials, such as DNA and other proteins. The process works by encouraging the desired protein to stick to a material that contains a ligand, a type of molecular glue. Each ligand is only attracted to certain parts of certain proteins. Having been separated from the mixture, the specific protein can now be obtained in purer form, facilitating its eventual use as a biotherapeutic.

The more selective the ligand is at binding to a specific protein, the more efficient the process is, and the less additional steps are required to produce the final drug. This results in reduced costs for the production of the drug. But despite its widespread use and benefits, there is very little understood about how the process actually works or how the ligands can be improved.

"We are trying to understand what exactly is making these materials so useful for separating proteins," Cramer said. "And what we are looking to uncover are the fundamental interactions within the chromatographic process that make the separations possible and efficient."

For this study, the researchers used several of the advanced research facilities within CBIS. Using the Microbiology and Fermentation Core, Cramer and his colleagues grew several mutants of a protein called ubiquitin. This group of modified proteins is referred to as a protein library.

To compare the difference between multimodal systems and more traditional chromatography, the team ran the library through a less sophisticated chromatography system called ion exchange chromatography, as well as the multimodal system. They found that there was very little to no difference in the binding of proteins to ligands in the traditional ion exchange system. In contrast, there were huge fluctuations in the binding of some of the different mutants within the multimodal system.

To delve further into why this happened, they input ubiquitin and the multimodal ligands into the massive 800 megahertz NMR at Rensselaer's CBIS. The NMR uses magnetic properties within organic materials to provide information on the minute molecular chemical properties of the material. From the NMR data, they were able to determine what part and type of the protein the ligands were binding to and how strongly they would bind. Their results validated the previous multimodal chromatography comparison experiments, showing that each of the protein mutants that strongly fluctuated in their binding strength in the multimodal chromatographic system were also the same ones identified with the NMR.

"This research is helping us develop a fundamental understanding of selectivity," Cramer said. Working with his team, Cramer will work to design improved ligands and improved processes for their purification.


'/>"/>

Contact: Gabrielle DeMarco
demarg@rpi.edu
518-276-6542
Rensselaer Polytechnic Institute
Source:Eurekalert  

Related biology news :

1. New lab manual focuses on essential methods for purifying and characterizing proteins
2. Membrane-coat proteins: Bacteria have them too
3. Rensselaer professor uncovers mysterious workings of cholera bacteria
4. Left or right? Early clues to soccer penalty kicks revealed at Rensselaer Polytechnic Institute
5. Rensselaer Polytechnic Institute professor Peter M. Tessier named Pew Scholar
6. Rensselaer Polytechnic Institute professor Patrick Underhill receives NSF CAREER award
7. Rensselaer Polytechnic Institute wins $2.45 million grant to support stem cell research
8. Rensselaer researchers to send bacteria into orbit aboard space shuttle Atlantis
9. Rensselaer leads effort to replace 1 of the most widely used drugs in American hospitals
10. Rensselaer receives more than $2 million from New York State to fund stem cell research
11. Trustee makes donation to start new solar energy research center at Rensselaer
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Purifying proteins: Rensselaer researchers use NMR to improve drug development
(Date:3/30/2017)... 2017 The research team of The Hong ... fingerprint identification by adopting ground breaking 3D fingerprint minutiae recovery and ... speed and accuracy for use in identification, crime investigation, immigration control, ... ... A research team led ...
(Date:3/27/2017)... , March 27, 2017  Catholic Health ... and Management Systems Society (HIMSS) Analytics for achieving ... Adoption Model sm . In addition, CHS previously ... U.S. hospitals using an electronic medical record (EMR). ... its high level of EMR usage in an ...
(Date:3/23/2017)... Research and Markets has announced the addition of the ... Forecast to 2025" report to their offering. ... The Global Vehicle Anti-Theft System ... over the next decade to reach approximately $14.21 billion by 2025. ... forecasts for all the given segments on global as well as ...
Breaking Biology News(10 mins):
(Date:5/23/2017)... ... May 23, 2017 , ... ... as Vice President of Clinical Operations. She brings years of expertise in establishing ... From her professional foundation as a licensed occupational therapist, through a variety of ...
(Date:5/22/2017)... ... 2017 , ... Stratevi, a boutique firm that partners with healthcare companies to ... an office in downtown Boston at 745 Atlantic Ave. , “We are seeing ... evidence on the value they provide, not just to patients, but also payers. Having ...
(Date:5/21/2017)... ... 20, 2017 , ... CNSDose is a genetically driven, clinically ... by finding the right antidepressant faster. CNSDose speeds recovery and reduces side ... personalized approach to treatment. , A peer-reviewed and published, 12-week double-blind ...
(Date:5/18/2017)... ... 18, 2017 , ... Lajollacooks4u has added another option for ... team-building package designed for groups of 10-30 people. Guests can choose their ... such as Blackened Shrimp with Edamame Salad, Pizza Rolls with Pepperoni and Mushrooms ...
Breaking Biology Technology: