Unnatural Amino Acid Engineering for Intracellular Delivery of Protein Therapeutics.

Autor:	Chen W; Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA., Sullivan MO; Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA. msulliva@udel.edu.
Jazyk:	angličtina
Zdroj:	Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2024; Vol. 2720, pp. 151-164.
DOI:	10.1007/978-1-0716-3469-1_11
Abstrakt:	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. (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze:	MEDLINE
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