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Related Concept Videos

Antibody Structure01:10

Antibody Structure

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Overview
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.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
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Antibody Structure and Classes01:25

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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.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
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Phase II Conjugation Reactions: Overview01:14

Phase II Conjugation Reactions: Overview

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Conjugation, a key component of phase II biotransformation reactions, is a vital process in drug detoxification. It involves transferring endogenous substances like glucuronic acid, sulfate, and glycine to drugs or their metabolites formed in phase I reactions. These conjugation reactions, often catalyzed by specific enzymes, transform potentially harmful metabolites into inactive, water-soluble forms easily excreted in urine or bile. By enhancing polarity and eliminating pharmacological...
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Related Experiment Video

Updated: Jul 5, 2025

Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting
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In-Depth Structure and Function Characterization of Heterogeneous Interchain Cysteine-Conjugated Antibody-Drug

Huijie Chen1, Danye Qiu2, Jian Shi1

  • 1Analytical Sciences, WuXi Biologics, 31 Yiwei Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.

ACS Pharmacology & Translational Science
|January 17, 2024
PubMed
Summary
This summary is machine-generated.

This study offers a comprehensive structural analysis of antibody-drug conjugates (ADCs), detailing conjugation and charge variants. The findings provide essential guidance for characterizing ADCs and developing next-generation cancer therapies.

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Area of Science:

  • Biochemistry
  • Analytical Chemistry
  • Oncology

Background:

  • Antibody-drug conjugates (ADCs) are advanced biologics for cancer therapy.
  • Comprehensive structural characterization of ADC variants remains limited.
  • Understanding ADC heterogeneity is crucial for drug development.

Purpose of the Study:

  • To perform a holistic characterization of an interchain cysteine-conjugated ADC.
  • To investigate conjugation and charge heterogeneity in ADCs.
  • To correlate structural properties with in vitro biological activities.

Main Methods:

  • Bottom-up and top-down analytical approaches were employed.
  • Conjugation mapping identified positional isomers and conjugation sites.
  • Capillary isoelectric focusing-mass spectrometry (cIEF-MS) was utilized for detailed analysis.

Main Results:

  • Positional isomer composition and conjugation process insights were obtained.
  • Charge heterogeneity origins and functional impacts were elucidated.
  • cIEF-MS successfully decoded PTMs, drug load, and isomer distribution.

Conclusions:

  • This study provides a general framework for in-depth ADC characterization.
  • The analytical findings support the discovery and development of novel ADCs.
  • Detailed structural insights enhance the understanding of ADC physicochemical and biological properties.