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An emerging strategy in immunotherapy involves the use of synthetic small molecules to engage, redirect, or leverage the immune system for a therapeutic effect such as anticancer activity. The TBD contains a cancer receptor ligand such as glutamate urea lysine (GUL), which can bind to the highly expressed prostate-specific membrane antigen (PSMA) receptor on prostate tumors.
Antibody-labeling reaction kinetics were studied using CIRs (CIR1/CIR4) equipped with desthiobiotin (an analog of biotin) to serve as a model TBD with nearinfinite binding affinity for a target receptor. This enables sufficiently high CIR binding affinity to streptavidin-coated probes to efficiently monitor “on-probe” antibody-labeling kinetics without concern for CIR dissociation from the probe. The CIR4 only differs from CIR1 through a shorter and more rigid linker between the ALD and ABD.