Navigation Links
Purifying proteins: Rensselaer researchers use NMR to improve drug development

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
Rensselaer Polytechnic Institute

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:
Related Image:
Purifying proteins: Rensselaer researchers use NMR to improve drug development
(Date:10/29/2015)... Oct. 29, 2015  Rubicon Genomics, Inc., today ... distribution of its DNA library preparation products, including ... new ThruPLEX Plasma-seq kit. ThruPLEX Plasma-seq has been ... of NGS libraries for liquid biopsies--the analysis of ... prognostic applications in cancer and other conditions. Eurofins ...
(Date:10/27/2015)... 27, 2015 Munich, Germany ... Mapping technology (ASGM) automatically maps data from mobile eye ... , so that they can be quantitatively analyzed ... Munich, Germany , October 28-29, 2015. SMI,s ... from mobile eye tracking videos created with SMI,s ...
(Date:10/23/2015)... DUBLIN , Oct. 23, 2015 Research ... of the "Global Voice Recognition Biometrics Market 2015-2019" ... --> --> The global voice recognition ... during 2014-2019. --> ... 2015-2019, has been prepared based on an in-depth market ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... ... maintain healthy metabolism. But unless it is bound to proteins, copper is also ... Health (NIH), researchers at Worcester Polytechnic Institute (WPI) will conduct a systematic study ...
(Date:11/24/2015)... , Nov. 24, 2015  Clintrax Global, Inc., a worldwide ... Carolina , today announced that the company has set a ... a 391% quarter on quarter growth posted for Q3 of 2014 ... and Mexico , with the establishment of ... December 2015. --> United Kingdom and ...
(Date:11/24/2015)... ... November 24, 2015 , ... The Academy of Model ... Group (SIG), MultiGP, also known as Multirotor Grand Prix, to represent the First–Person View ... years. Many AMA members have embraced this type of racing and several new model ...
(Date:11/24/2015)... Israel , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) ... on December 29, 2015 at 11:00 a.m. Israel ... Electra Tower, 98 Yigal Allon Street, 36 th Floor, ... of Eric Paneth and Izhak Tamir to the ... Rami Skaliter as external directors; , approval of an amendment to ...
Breaking Biology Technology: