title: Interior surface modification of bacteriophage MS2.
abstract: An efficient strategy for the interior surface functionalization of MS2 viral capsids is reported, featuring a new hetero-Diels-Alder bioconjugation reaction. After virus isolation, the RNA genome was removed from the spherical particles by exposure to pH 11.8 conditions for a period of 4 h. Following this, 180 tyrosine residues on the interior surface of each "empty" capsid shell were modified by using a site-selective diazonium-coupling reaction. To attach additional functionality, the azo conjugate was reduced with Na2S2O4 to afford an ortho-amino tyrosine derivative. Oxidation of this moiety with NaIO4 produced an o-iminoquinone on the protein surface, which was found to undergo an efficient hetero-Diels-Alder reaction with N-(4-aminophenyl)acrylamide. This four-step procedure can be carried out in under 4 h, reaches high levels of conversion, and yields the desired conjugates in >60% overall yield.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.forename: Ernest W
authors.initials: EW
authors.lastname: Kovacs
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Francis
mesh_terms: D019149:Bioreactors; D002213:Capsid / Q000737:chemistry; D036022:Capsid Proteins / Q000032:analysis*; D004926:Escherichia coli / Q000821:virology; D017909:Levivirus / Q000737:chemistry* / Q000302:isolation & purification; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D012367:RNA, Viral / Q000032:analysis*
chemical_list: D036022:Capsid Proteins; D012367:RNA, Viral