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Related Experiment Video

Updated: Jul 18, 2025

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Published on: March 6, 2019

Site-Specific Antibody Conjugation Using Modified Bisected N-Glycans: Method Development and Potential toward Tunable

Yen-Pang Hsu¹, Omar Nourzaie², Ariel E Tocher³

¹MRL, Merck & Co., Inc., 320 Bent St., Cambridge, Massachusetts 02141, United States.

Bioconjugate Chemistry

|August 24, 2023

Summary

A novel glycan-bridged conjugation strategy enables site-specific antibody-drug conjugates (ADCs) creation without complex antibody modification. This method effectively targets HER2-expressing cancer cells and allows for glycoengineering to optimize ADC properties.

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Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction

Published on: September 14, 2018

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Last Updated: Jul 18, 2025

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Published on: March 6, 2019

Efficient and Site-specific Antibody Labeling by Strain-promoted Azide-alkyne Cycloaddition

Efficient and Site-specific Antibody Labeling by Strain-promoted Azide-alkyne Cycloaddition

Published on: December 23, 2016

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction

Published on: September 14, 2018

Area of Science:

Bioconjugation Chemistry
Immunology
Oncology

Background:

Antibody-drug conjugates (ADCs) are crucial therapeutics due to their target specificity and potency.
Existing ADC conjugation strategies often require complex antibody engineering.
There is a need for advanced conjugation methods offering improved biocompatibility and controlled biophysical properties.

Purpose of the Study:

To develop a novel site-specific conjugation strategy for ADCs using a bisecting glycan bridge.
To demonstrate the efficacy of this strategy in creating anti-HER2 ADCs.
To explore the potential for glycoengineering to modulate ADC properties.

Main Methods:

A bisecting glycan-bridged conjugation approach was employed, bypassing the need for oligosaccharide synthesis or genetic antibody engineering.
Human and mouse anti-HER2 IgGs were conjugated with monomethyl auristatin E using this strategy.
The stability of the glycan bridge and the efficacy of the resulting ADCs against HER2-expressing cancer cells were evaluated.

Main Results:

The glycan-bridged conjugation strategy enabled site-specific antibody modification.
The developed ADCs demonstrated excellent stability and effectively eliminated HER2-expressing cancer cells.
The strategy proved compatible with glycan structure remodeling for potential glycoengineering.

Conclusions:

The bisecting glycan-bridged conjugation strategy offers a versatile and efficient method for creating site-specific ADCs.
This approach facilitates the development of potent and stable ADCs with tunable pharmacokinetic and immunogenic profiles.
The method holds promise for advancing ADC-based cancer therapies through simplified conjugation and glycoengineering.