4.3 Diversifying the nanomaterials that can be synthesized on TMV/BSMV-derived biotemplates
While TMV/BSMV virions and VLPs serve as exceptional biotemplates for metal mineralization, they are not directly compatible for the synthesis of non-metallic nanomaterials. However, the introduction of surface-accessible amino acids, including aspartate, glutamate, and tyrosine provide conjugation sites for synthesis of non-metallic nanomaterials via covalent bonding. For example, the carboxylic acid moiety of aspartate and glutamate can react with amines, which have been functionalized with biotin, chromophores, and crown ethers while tyrosine can conjugate with PEG [73]. These conjugations enable medical applications of TMV such as vectors for drug delivery.
In addition to canonical amino acids, synthetic noncanonical amino acids with unique functional groups have also been incorporated in other VLPs such as hepatitis B virus (HBV) or bacteriophage Qβ to expand coating capabilities further [74]. Noncanonical amino acids provide unique functional groups, such as alkynes and aminophenylalanine, that facilitate bioorthogonal coating [75]. Bioorthogonal reactions enable specific conjugation via the noncanonical amino acids without cross-reaction with canonical amino acids of the virions/VLPs, reducing the risk of disrupting the physicochemical properties that drive biotemplate self-assembly. Alkyne-containing noncanonical amino acids have been incorporated into virions to attach PEG, oligonucleotides, antibody fragments, and other peptides via click chemistry [74] while aminophenylalanine incorporated VLPs have been used to conjugate cell type-specific targeting peptides, enabling drug delivery to specific cell types [76]. The number of novel viral-derived biomaterials are certain to expand further as new noncanonical amino acids are engineered and incorporated into CPs [77].