On-virus construction of polyvalent glycan ligands for cell-surface receptors

Glycans arrayed on the exterior of virus particles were used as substrates for glycosyltransferase reactions to build di- and trisaccharides from the virus surface. The resulting particles exhibited tight and specific associations with cognate receptors on beads and cells, in one example defeating in cis cell-surface interactions in a manner characteristic of polyvalent binding. Combined with the ability of viruses to provide structurally well-defined attachment points, the methodology provides a convenient and powerful way to prepare complex carbohydrate ligands for clustered receptors.     

Aldolase antibody activation of prodrugs of potent aldehyde-containing cytotoxics for selective chemotherapy

Prodrugs of potent aldehyde analogues of the anticancer drug doxorubicin (Dox) were synthesized. These prodrugs were efficiently activated by antibody 93F3 and no drug formation was observed in the absence of 93F3 in either phosphate buffered saline or cell culture media. In the presence of antibody 93F3, these prodrugs were activated and decreased the proliferation of human cancer cells in in vitro proliferation assays.     

Virus-glycopolymer conjugates by copper(I) catalysis of atom transfer radical polymerization and azide-alkyne cycloaddition

The Cu(I)-catalyzed ATRP and azide-alkyne cycloaddition reactions together provide a versatile method for the synthesis of end-functionalized glycopolymers and their attachment to a suitably modified viral protein scaffold.     

Natural supramolecular building blocks. Wild-type cowpea mosaic virus

Cowpea mosaic virus (CPMV) can be isolated in gram quantities, possesses a structure that is known to atomic resolution, and is quite stable. It is therefore of potential use as a molecular entity in synthesis, particularly as a building block on the nanochemical scale. CPMV was found to possess a lysine residue with enhanced reactivity in each asymmetric unit, and thus 60 such lysines per virus particle. The identity of this residue was established by a combination of acylation, protein digestion, and mass spectrometry. Under forcing conditions, up to four lysine residues per asymmetric unit can be addressed. In combination with engineered cysteine reactivity described in the accompanying paper, this provides a powerful platform for the alteration of the chemical and physical properties of CPMV particles.     

Multivalent, bifunctional dendrimers prepared by click chemistry

Unsymmetrical dendrimers, containing both mannose binding units and coumarin fluorescent units, have been prepared using click chemistry and shown to be highly efficient, dual-purpose recognition/detection agents for the inhibition of hemagglutination.