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].