Chemical Modification of Viruses and Virus-Like Particles

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Protein capsids derived from viruses may be modified by methods, generated, isolated, and purified on large scales with relative ease. In recent years, methods for their chemical derivatization have been employed to broaden the properties and functions accessible to investigators desiring monodisperse, atomic-resolution structures on the nanometer scale. Here we review the reactions and methods used in these endeavors, including the modification of lysine, cysteine, and tyrosine side chains, as well as the installation of unnatural amino acids, with particular attention to the special challenges imposed by the polyvalency and size of virus-based scaffolds.