Confirming Antibody-Based Drugs | Chemical & Engineering News
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Web Date: August 12, 2014

Confirming Antibody-Based Drugs

ACS Meeting News: Measuring disulfide pattern via collision induced unfolding, ion mobility, could lead to new tool for quality control
Department: Science & Technology
News Channels: Analytical SCENE
Keywords: Antibody, ion mobility, mass spectrometry, disulfide bonds, ACS meeting

Antibody-based drugs to fight cancer, viral diseases such as Ebola, and many other serious health threats are on the rise. Because subtle structural changes can alter their specificity, there’s a need for analytical methods that ensure that antibody-based drugs have the desired structure.

A new way to characterize the disulfide bonds that hold antibodies together could help fill that need, reported Brandon T. Ruotolo of the University of Michigan, Ann Arbor, at the American Chemical Society national meeting this week in San Francisco. He described the method, which relies on collision-induced unfolding and ion mobility spectroscopy, in a symposium sponsored by the Division of Analytical Chemistry.

In the method, Ruotolo and his coworkers select an individual charge state of a gas-phase antibody and heat it via gas-phase collisions, which cause it to unfold. They measure the size of the unfolded states with ion mobility.

By measuring the unfolding products as a function of the collisional heating, they can track the unfolding trajectory for the intact antibody. The number and size of the unfolded species form a fingerprint that is unique to the original isolated ion. By comparing the gas-phase unfolding for an analyte antibody to that of a reference antibody, they can quickly determine whether they match. Such a method could be used as a quality-control tool to make sure that an antibody drug has the correct structure.

The unfolding method is “clever and could be developed as a useful tool for the biopharm industry,” said Joseph A. Loo, a biochemistry professor and mass spectrometrist at the University of California, Los Angeles. “But in order for it to be truly useful, the method needs to have the structural resolution to discern all of the possibilities in the disulfide patterns.”

Ruotolo acknowledges that the method, while promising, still struggles with determining the position of disulfide bonds. For that, “you probably still have to resort to a more classical sequencing approach,” he told C&EN.

Ruotolo hopes to convince biopharmaceutical companies to help test the method. He is currently involved in a collaboration with Amgen to see if collision-induced unfolding coupled with ion mobility/mass spectrometry can differentiate mixed populations of properly folded Y-shaped antibodies and improperly folded T-shaped ones.

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