ArticleMethods in molecular biology (Clifton, N.J.)2024
Unnatural Amino Acid Engineering for Intracellular Delivery of Protein Therapeutics.
Article in Methods in molecular biology (Clifton, N.J.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Protein drugs are a critically important therapeutic modality due to the sophisticated binding recognition, catalytic properties, and disease relevance of proteins. There is a clear need for new strategies able to improve pharmacokinetics, bioavailability, and/or intracellular delivery of therapeutic proteins, as stability limitations have significantly hindered clinical advancement, and most proteins are membrane impermeable. Bioconjugation strategies able to site-specifically modify proteins with cell binding, and other ligands offer a particularly valuable approach to facilitate protein delivery due to the importance of ligand presentation on protein bioactivity and cellular uptake. We explored unnatural amino acid (UAA) incorporation as a novel strategy to tunably incorporate clustered cell-binding ligands in fluorescent proteins and suicide enzymes, resulting in substantial increases in cell-specific uptake and targeted cell-killing activity. These approaches offer a valuable and versatile method to modify a variety of proteins and enable improved clinical potential.
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