Putting peptide coats on virus shells could lead to targeted medical imaging in cancer diagnostics, according to US chemists.

Matthew Francis, at the University of California, in Berkeley, and his colleagues have attached different peptides to the outer shell (capsid) of an icosahedrally-shaped virus particle called bacteriophage MS2. The group has previously used such capsids to house gadolinium complexes, which have applications in medical imaging. With the aim of eventually building targeted imaging agents, the group attached the capsids to peptides that target different human tissues, including a breast cancer cell line.

Peptides are attached to viral capsids through unnatural amino acids (left)

Bacteriophage MS2 particles are formed by the self-assembly of 180 copies of a single protein monomer. Francis's team used Escherichia coli bacteria to express mutants of this protein that included a single para-amino-L-phenylalanine group per monomer. From several mutants, the researchers chose the one that formed in the highest yield, which held the included groups on the capsid's outer surface. The team then used oxidative bioconjugation reactions to couple each peptide in turn to these surface groups and found that the capsids remained intact.

According to Francis, peptide coupling to protein structures such as bacteriophage MS2 is 'a particularly difficult challenge, because the reactions used for this purpose must proceed site-selectively in the presence of the full set of amino acid functional groups.' Also, modifying the proteins after they are made means many more, non-biocompatible groups can be incorporated.

Looking to the future, Francis suggested that his peptide coupling method could find applications in both biochemical and materials science fields. His team is currently investigating the modified capsids' abilities to target tumours in vivo.

David Parker