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Related Concept Videos

Phase II Reactions: Sulfation and Conjugation with α-Amino Acids01:19

Phase II Reactions: Sulfation and Conjugation with α-Amino Acids

Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme activation, sulfur...

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Quantification of Site-specific Protein Lysine Acetylation and Succinylation Stoichiometry Using Data-independent Acquisition Mass Spectrometry
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Quantification of Site-specific Protein Lysine Acetylation and Succinylation Stoichiometry Using Data-independent Acquisition Mass Spectrometry

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Protocols for lysine conjugation.

Marie-Priscille Brun1, Laurence Gauzy-Lazo

  • 1Natural Product and Protein Chemistry, Sanofi, Vitry-sur-Seine, France.

Methods in Molecular Biology (Clifton, N.J.)
|August 6, 2013
PubMed
Summary
This summary is machine-generated.

This chapter details methods for creating antibody-drug conjugates (ADCs) by linking drugs to lysine residues on antibodies. These techniques support various cancer therapies using diverse cytotoxic agents and linker types.

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Area of Science:

  • Bioconjugation Chemistry
  • Pharmaceutical Sciences
  • Oncology

Background:

  • Antibody-drug conjugates (ADCs) are crucial therapeutics in targeted cancer treatment.
  • Current ADC development primarily utilizes conjugation strategies involving lysine or cysteine residues.
  • Efficient and versatile conjugation methods are essential for advancing ADC technology.

Purpose of the Study:

  • To describe chemical methodologies for preparing ADCs via lysine residue conjugation.
  • To present adaptable methods applicable to a range of cytotoxic drugs and linker chemistries.
  • To provide a resource for researchers developing novel antibody-drug conjugates.

Main Methods:

  • Conjugation of drugs to solvent-exposed ε-amino groups of lysine residues on monoclonal antibodies.
  • Application of methods to various cytotoxic agents, including tubulin binders and DNA-targeting agents.
  • Utilizing diverse linker types, such as cleavable and non-cleavable, peptidic, and disulfide-based linkers.

Main Results:

  • Demonstrated feasibility of ADC preparation through lysine conjugation.
  • Showcased the versatility of the described methods across different drug payloads and linker designs.
  • Established a foundation for the development of novel ADC therapeutics.

Conclusions:

  • Lysine conjugation offers a viable and adaptable strategy for antibody-drug conjugate synthesis.
  • The described methods support the development of ADCs with diverse payloads and linker technologies.
  • Advancements in conjugation chemistry are key to expanding the therapeutic potential of ADCs.