A hydrazide PEG (polyethylene glycol) linker is used in bioconjugation and drug delivery to enhance the solubility, stability, and targeted delivery of therapeutic and diagnostic molecules.
Components
- PEG: A hydrophilic polymer that improves solubility and stability while extending drug circulation time.
- Hydrazide Group: Contains -NH-NH₂ linked to a carbonyl group, reacting with carbonyls to form stable hydrazone bonds, ideal for conjugation.
Functionality
- Conjugation Chemistry: Forms stable hydrazone bonds with carbonyl groups, enabling versatile attachment of drugs, peptides, and proteins.
- Linker Properties: Enhances solubility, reduces nonspecific interactions, and improves biocompatibility.
Applications
- Drug Delivery: PEGylates drugs to improve solubility, stability, and half-life; enables targeted and controlled release.
- Protein and Peptide Conjugation: Allows site-specific labeling and enhancement of therapeutic proteins.
- Diagnostics and Imaging: Attaches imaging agents or probes for detection and imaging.
A hydrazide PEG linker is used in bioconjugation to create stable, site-specific attachments between biomolecules. For example, in the antibody-drug conjugate (ADC) Adcetris (brentuximab vedotin), a hydrazone linkage is employed. This linker connects the cytotoxic drug monomethyl auristatin E (MMAE) to the antibody targeting CD30. The hydrazone bond allows for stable circulation in the bloodstream while enabling controlled drug release inside the target cancer cells, enhancing therapeutic efficacy and reducing off-target effects.
Considerations
- Reaction Conditions: Requires specific pH and carbonyl group presence for bond formation.
- Stability: Hydrazone bonds are generally stable but can be affected by environmental factors.
In summary, hydrazide PEG linkers are versatile tools that enhance the performance of biomolecules in drug delivery, imaging, and biochemical research.
Ref:
Ultimate Guide to Choosing the Right Cleavable Linker for ADCs
Cleavable Linkers Play a Pivotal Role in the Success of Antibody-Drug Conjugates (ADCs)
u, Z., Li, S., Han, S. et al. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Sig Transduct Target Ther 7, 93 (2022). https://doi.org/10.1038/s41392-022-00947-7.
