Closer look at unexamined interactions could improve drug purification
process
Rensselaer engineers aim to make better biopharmaceuticals through deeper analysis

Date:
November 3, 2021
Source:
Rensselaer Polytechnic Institute
Summary:
Research explores the fundamentals of how different molecules
interact with various surfaces during the purification process.



FULL STORY ==========================================================================
The process of purifying biopharmaceutical drugs remains a costly and
time- consuming challenge. A deeper understanding of how unwanted elements within biomanufactured proteins bind to the molecules developed to remove
them could help researchers make purity processes more efficient, more
complex, and increasingly scalable.


==========================================================================
In research published in Langmuir, a team led by Steven Cramer, an endowed chair professor of chemical and biological engineering at Rensselaer Polytechnic Institute, explored the fundamentals of how different
molecules interact with various surfaces during the purification process.

Cramer is a leading expert in chromatographic bioprocessing, a separation technique used in biopharmaceutical purification to selectively choose
which components of a protein mixture should be kept and which components should be removed. Ions or molecules, known as ligands, are developed
to bind to specific components that should either be saved or discarded
during this process.

"This is part of a very big effort to understand the fundamentals of
how these molecules interact with surfaces," said Cramer, a member of
the Rensselaer Center for Biotechnology and Interdisciplinary Studies
(CBIS), where the work was performed. "Our group is trying to ramp up the intellectual level of this kind of analysis in a variety of ways." This
new paper builds upon research by the Cramer Lab recently published in Biotechnology and Bioengineering. In that work, researchers used nuclear magnetic resonance (NMR) spectroscopy and complex computer simulations
to examine the fundamentals of how different molecules interact with
various surfaces and ligands, including how and where binding happens,
and if certain molecular interactions affect the binding process.

Working with Merck Pharmaceuticals and Bio-Rad Laboratories and using
the NMR core facility in CBIS run by co-author Scott McCallum, the
team looked at the Fc part of an IgG1 antibody and how ligands interact
with that section of the antibody protein in particular. (If you were to picture an antibody looking like the letter "Y," the Fc part would be the tail.) IgG1 antibodies are used in a large majority of biopharmaceutical
drugs, meaning a deeper understanding of how their components interact
with various molecules and ligands could have widespread implications.

In the Langmuir paper, the team took its exploration even deeper by
adding nanoparticles to the surface of various proteins in order to see
exactly where the ligands were binding.

"With this approach, we can then also look at some of the subtle
interactions that are happening," Cramer said. "Sometimes these ligands
come together and form these clusters of ligands, and these clusters
actually drastically change the behavior." This work, Cramer said, could
lead to the development of new and improved materials and ligands. It
also could help researchers develop more nuanced and specific ways of separating out unwanted molecules that are very similar to another type
of molecule that needs to remain. All of these advancements could improve
the drug purification process, making it more efficient and effective.

========================================================================== Story Source: Materials provided by
Rensselaer_Polytechnic_Institute. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Ronak B. Gudhka, Mayank Vats, Camille L. Bilodeau, Scott
A. McCallum,
Mark A. McCoy, David J. Roush, Mark A. Snyder, Steven
M. Cramer. Probing IgG1 FC-Multimodal Nanoparticle Interactions:
A Combined Nuclear Magnetic Resonance and Molecular Dynamics
Simulations Approach. Langmuir, 2021; 37 (41): 12188 DOI:
10.1021/acs.langmuir.1c02114 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211103155125.htm

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