Related Experiment Video
Updated: Feb 11, 2026
12:15
Generation of Monoclonal Antibodies Against Natural Products
Published on: April 6, 2019
11.6K
Mechanically interlocked functionalization of monoclonal antibodies
Krzysztof P Bzymek1, James W Puckett1, Cindy Zer1
1Department of Molecular Medicine, Beckman Research Institute of City of Hope, 1710 Flower St., Duarte, CA, 91010, USA.
Nature Communications
|April 22, 2018
Summary
Researchers developed a novel method to quickly attach various functionalities to monoclonal antibodies (mAbs). This "snapping" technique enhances antibody-drug conjugates and theranostic agents for improved cancer therapies.
Area of Science:
- Biochemistry
- Chemical Biology
- Immunology
Background:
- Monoclonal antibodies (mAbs) are highly specific and possess favorable pharmacokinetic properties, making them ideal scaffolds for targeted therapies.
- Functionalizing mAbs with payloads like cytotoxins, biologics, or imaging agents is crucial for therapeutic and theranostic applications.
- Existing functionalization methods can be complex and time-consuming, limiting the rapid development of novel antibody conjugates.
Purpose of the Study:
- To develop an efficient and rapid method for functionalizing monoclonal antibodies (mAbs) using a novel meditope-Fab interaction.
- To enhance the affinity and stability of the meditope-Fab complex through structural insights and mechanical interlocking.
- To demonstrate the utility of this functionalization strategy for creating targeted therapeutic and theranostic agents.
Main Methods:
- Engineered a meditope-Fab interaction with significantly enhanced affinity and extended complex lifetime.
- Incorporated a mechanical bond via click chemistry, using an azide on the meditope threaded through the Fab region.
- Validated the functionalized mAb complex's ability to retain antigen specificity and perform in vivo tumor imaging in a mouse model.
Main Results:
- Achieved a four-order-of-magnitude increase in meditope-Fab interaction affinity and lifetime.
- Successfully created a mechanically interlocked meditope-Fab complex with improved stability.
- Demonstrated that the functionalized mAb complex maintains antigen specificity and enables successful tumor imaging in mice.
Conclusions:
- The developed method allows for rapid and versatile functionalization of monoclonal antibodies, akin to "snapping" components into place.
- This approach facilitates the swift creation of diverse mAb-payload combinations for potential therapeutic and theranostic applications.
- The mechanically interlocked complex represents a significant advancement in antibody engineering for targeted medicine.
Related Concept Videos
01:58Mechanical Protein Functions
5.7K
Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.
5.7K
01:58Mechanical Protein Function
2.5K
2.5K
01:10Antibody Structure
65.7K
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...
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...
65.7K
03:06Reaction Mechanisms
31.2K
Chemical reactions often occur in a stepwise fashion, involving two or more distinct reactions taking place in a sequence. A balanced equation indicates the reacting species and the product species, but it reveals no details about how the reaction occurs at the molecular level. The reaction mechanism (or reaction path) provides details regarding the precise, step-by-step process by which a reaction occurs.
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
31.2K
01:26Antibody Actions
2.9K
Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
2.9K
02:45The Quantum-Mechanical Model of an Atom
59.7K
Shortly after de Broglie published his ideas that the electron in a hydrogen atom could be better thought of as being a circular standing wave instead of a particle moving in quantized circular orbits, Erwin Schrödinger extended de Broglie’s work by deriving what is now known as the Schrödinger equation. When Schrödinger applied his equation to hydrogen-like atoms, he was able to reproduce Bohr’s expression for the energy and, thus, the Rydberg formula governing hydrogen spectra.
59.7K