| The protein coats encompassing many viruses have proven to be useful in a variety of materials applications, due to their ease of isolation, well-characterized self-assembly, and precise ordering of chemical functionality on nanometer length scales. We have developed modifications addressing both the external and internal surfaces of the tobacco mosaic virus coat protein, and are currently deploying them in an effort to synthesize novel functional materials.; TMV is a rod-shaped virus containing a solvent-accessible inner pore. This interior surface has been modified through amide formation between acidic amino acids and a variety of primary and secondary amines. Proteolytic digest has determined that the modification occurs at internal glutamates 97 and 106; this is, to our knowledge, the first example of covalent functionalization of the inner surface of TMV.; The external surface of the protein, in both its capsid form and as recombinant monomeric protein, has been modified through reaction with tyrosine residues. Reaction with a ketone-bearing diazonium salt leads to almost complete conversion to singly modified protein monomer, which can subsequently be targeted using a variety of aminooxy-functionalized small molecules. Proteolytic digest in this case isolated the site of modification as tyrosine 139, which has previously been shown to be modified selectively over the protein's other tyrosine residues.; We are currently developing methods to utilize externally modified coat protein for the lateral assembly of TMV aggregates, mediated by cyclodextrin binding. To that end, both a cyclodextrin appropriately functionalized for protein modification and a biscyclodextrin intended to interact with two ligand-bearing protein aggregates have been synthesized. |
