Linkers are molecules used to connect two different molecules together to form a larger, more complex structure. They are used in many scientific disciplines, including chemical synthesis, biochemistry, and pharmaceuticals. Two of the most common types of linkers are ADC linkers and PEG linkers.
The use of linkers in chemical synthesis is a common practice in many chemical laboratories. Linkers provide a means of connecting two molecules together in a specific and predictable manner. Two of the most commonly used linkers in the field of bioconjugation are the ADC linker and the PEG linker. While both are designed to bind two molecules together, they are quite different in terms of their structure, chemistry, and applications.
Antibody-drug conjugates (ADCs) are a class of cancer drugs that deliver a toxic payload directly to cancer cells by combining an antibody with a small molecule drug. In ADCs, the antibody targets the cancer cell and the small molecule drug provides the therapeutic effect. The key to an effective ADC is the linker, which connects the antibody to the small molecule drug. There are two main types of linkers used in ADCs: ADC linkers and polyethylene glycol PEG linkers.
ADC Linkers
The ADC linker, or amide di-Cys linker, is a short peptide linker consisting of two cysteine residues connected by an amide bond. This linker is commonly used to attach a small molecule to a peptide. The ADC linker is relatively stable and offers a high degree of control over the attachment of the small molecule to the peptide. It is also able to withstand high temperatures and is relatively resistant to enzymatic cleavage.
ADC linkers are typically cleavable, meaning that they can be broken down by enzymes in the body, releasing the small molecule drug. This allows the drug to be delivered directly to the cancer cell, where it can have its therapeutic effect. ADC linkers can be made from a variety of materials, including peptides, polymers, and small molecules. The choice of ADC linker will depend on the specific requirements of the drug, such as stability, release rate, and toxicity.
PEG Linkers
The PEG linker, or polyethylene glycol linker, is a hydrophilic polymer chain composed of repeating ethylene glycol units. This linker is commonly used to attach a large molecule, such as a protein or carbohydrate, to a small molecule.
PEG linkers, on the other hand, are non-cleavable and are used to increase the half-life of the ADC. PEG is a long chain of repeating units of ethylene glycol and is commonly used as a solubilizing agent in pharmaceuticals. When attached to the ADC, PEG increases the size of the molecule and slows down its clearance from the body, resulting in a longer half-life for the ADC. PEG linkers can also improve the stability of the ADC and prevent it from being recognized and eliminated by the body’s immune system.
Differences between ADC Linkers and PEG Linkers
The main difference between ADC linkers and PEG linkers is their function. ADC linkers are designed to release the small molecule drug directly into the cancer cell, while PEG linkers are designed to increase the half-life of the ADC. This means that ADC linkers are typically cleavable, while PEG linkers are non-cleavable. Additionally, ADC linkers can be made from a variety of materials, while PEG linkers are made from polyethylene glycol.
Both ADC linkers and PEG linkers have their own unique advantages and disadvantages. ADC linkers are easily conjugated to other molecules and are relatively stable, but they are not as efficient as PEG linkers. PEG linkers are more efficient and are easily attached to surfaces, proteins, and other molecules, but they are not as stable as ADC linkers. Ultimately, which type of linker is best for a specific application depends on the specific needs and goals of the project.
In conclusion, both ADC linkers and PEG linkers play important roles in the design and development of ADCs. ADC linkers are responsible for delivering the small molecule drug directly to the cancer cell, while PEG linkers are used to increase the half-life of the ADC. The choice of linker will depend on the specific requirements of the drug and will be carefully considered during the design and development process.