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High-Throughput Assessment of Structural Continuity in Biologics.


ABSTRACT: We demonstrate a high-throughput chemoprinting platform that confirms the consistency in the higher-order structure of protein biologics and is sensitive enough to detect single-point mutations. This method addresses the quality and consistency of the tertiary and quaternary structure of biologic drug products, which is arguably the most important, yet rarely examined, parameter. The method described uses specific small-molecule ligands as molecular probes to assess protein structure. Each library of probe molecules provides a "fingerprint" when taken holistically. After proof-of-concept experiments involving enzymes and antibodies, we were able to detect minor conformational perturbations between four 48 kDa protein mutants that only differ by one amino acid residue.

SUBMITTER: Musetti C 

PROVIDER: S-EPMC6349355 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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High-Throughput Assessment of Structural Continuity in Biologics.

Musetti Caterina C   Bean Mark F MF   Quinque Geoffrey T GT   Kwiatkowski Christopher C   Szewczuk Lawrence M LM   Baldoni John J   Zajac Matthew A MA  

Analytical chemistry 20180208 4


We demonstrate a high-throughput chemoprinting platform that confirms the consistency in the higher-order structure of protein biologics and is sensitive enough to detect single-point mutations. This method addresses the quality and consistency of the tertiary and quaternary structure of biologic drug products, which is arguably the most important, yet rarely examined, parameter. The method described uses specific small-molecule ligands as molecular probes to assess protein structure. Each libra  ...[more]

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2024-08-26 | GSE271332 | GEO