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Related Concept Videos

Antibody Structure01:10

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Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
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Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
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Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
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Generation of Monoclonal Antibodies Against Natural Products
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Monoclonal antibody higher order structure analysis by high throughput protein conformational array.

Yuanli Song1, Deqiang Yu1, Mukesh Mayani1

  • 1a Biologics Process Development, Bristol-Myers Squibb , 38 Jackson Road, Devens , MA , USA.

Mabs
|January 10, 2018
PubMed
Summary
This summary is machine-generated.

High-throughput protein conformational array (PCA) reveals structural differences in therapeutic antibodies. This method aids in understanding antibody higher order structure (HOS) and potential immunogenicity during development.

Keywords:
Biologics developmentHigh throughputHigher order structureMonoclonal antibodyProtein conformational array

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Area of Science:

  • Biochemistry
  • Protein Science
  • Immunology

Background:

  • Antibody higher order structure (HOS) is crucial for therapeutic efficacy and safety.
  • Understanding HOS aids in preventing compromised bioactivity and physicochemical properties.
  • Protein conformational array (PCA) is a novel technique for HOS determination.

Purpose of the Study:

  • To develop and apply a high-throughput multiplex PCA for HOS analysis.
  • To investigate structural differences between antibody subclasses and processing conditions.
  • To validate PCA technology using small-angle X-ray scattering.

Main Methods:

  • Developed a multiplex PCA with 48-fold higher throughput than ELISA-based PCA.
  • Analyzed structural differences in IgG1 and IgG4 subclasses.
  • Applied small-angle X-ray scattering for mechanistic insights and validation.

Main Results:

  • Revealed significant structural differences between IgG1 and IgG4 subclasses.
  • Demonstrated that antibody aggregation increases epitope exposure, potentially causing immunogenicity.
  • PCA data correlated well with traditional stability assays (SEC, PTSA).

Conclusions:

  • High-throughput PCA is effective for analyzing therapeutic antibody HOS.
  • PCA provides insights into antibody structure changes due to processing.
  • This method supports the discovery and development of safe and effective therapeutic antibodies.