The resulting particles have advantageous pharmacokinetics and strong binding to target cells in vitro. Experiments with mouse tumor models are in progress to explore the properties of the particles in vivo.
A New Method to Measure Biodistribution of Proteins
Our preparation of gadolinium-labeled viruses for magnetic resonance imaging led to the observation that the concentrations of such particles can be measured with exquisite accuracy and sensitivity via a spectroscopic method: inductively coupled plasma optical emission spectroscopy. Using this technique, we can follow the distribution of gadolinium-labeled particles in the blood and major organs of mice with great ease and without the use of hazardous radioactive labels or cumbersome fluorescence methods. Because stable complexes of gadolinium and other inert lanthanide elements can be readily attached to proteins in a variety of ways, we are exploring this method as a general pharmacokinetic tool.
New Chemically Modified Viruses
This past year, using hepatitis B coat protein and azidohomoalanine in place of methionine, we achieved the first incorporation of unnatural amino acids into a viruslike particle. This method will allow us to program with complete accuracy the placement of the azide group and then to affect the group with complete selectivity by using copper-catalyzed cycloaddition. Work is proceeding with both hepatitis B virus and the bacteriophage Qβ.
Dìaz, D.D., Finn, M.G. A facile synthesis of N,N′-bis[formamidine]ureas and symmetrical N,N.-disubstituted formamidines. Lett. Org. Chem. 2:398, 2005.
Dìaz, D.D., Lewis, W.G., Finn, M.G. Acid-mediated amine exchange of N,N-dimethylformamidines: preparation of electron-rich formamidines. Synlett 2214, 2005, Issue 14.
Dìaz, D.D., Lewis, W.G., Finn, M.G. Activation of urea as a leaving group in substitution reactions of formamidine ureas. Chem. Lett. 34:78, 2005.
Dìaz, D.D., Ripka, A.S., Finn, M.G. 1-(tert-Butylimino-methyl)-1,3-dimethyl-urea hydrochloride. Org. Synth. 82:59, 2005.
Gissibl, A., Finn, M.G., Reiser, O. Cu(II)-aza(bisoxazoline)-catalyzed asymmetric benzoylations. Org. Lett. 7:2325, 2005.
Keller, K.A., Guo, J., Punna, S., Finn, M.G. A thermally-cleavable linker for solid-phase synthesis. Tetrahedron Lett. 46:1181, 2005.
Meng, J., Fokin, V.V., Finn, M.G. Kinetic resolution by copper-catalyzed azide-alkyne cycloaddition. Tetrahedron Lett. 46:4543, 2005.
Narayan, S., Muldoon, J., Finn, M.G., Fokin, V.V., Kolb, H.C., Sharpless, K.B. On water: unique reactivity of organic compounds in aqueous suspension. Angew. Chem. Int. Ed. 44:3275, 2005.
Punna, S., Kuzelka, J., Wang, Q., Finn, M.G. Head-to-tail peptide cyclodimerization by copper-catalyzed azide-alkyne cycloaddition. Angew. Chem. Int. Ed. 44:2215, 2005.
Rae, C.S., Wei Khor, I., Wang, Q., Destito, G., Gonzalez, M.J., Singh, P., Thomas, D.M., Estrada, M.N., Powell, E., Finn, M.G., Manchester, M. Systemic trafficking of plant virus nanoparticles in mice via the oral route. Virology 343:224, 2005.
Rodionov, V.O., Fokin, V.V., Finn, M.G. Mechanism of the ligand-free Cu(I)-catalyzed azide-alkyne cycloaddition reaction. Angew. Chem. Int. Ed. 44:2210, 2005.
Sen Gupta, S., Raja, K.S., Kaltgrad, E., Strable, E., Finn, M.G. Virus-glycopolymer conjugates by copper(I) catalysis of atom transfer radical polymerization and azide-alkyne cycloaddition. Chem. Commun. (Camb.) 4315, 2005, Issue 34.
Strable, E., Johnson, J.E., Finn, M.G . Natural nanochemical building blocks: icosahedral virus particles organized by attached oligonucleotides. Nano Lett. 4:1385, 2004.
Stray, S.J., Bourne, C.R., Punna, S., Lewis, W.G., Finn, M.G., Zlotnick, A. A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly. Proc. Natl. Acad. U. S. A. 102:8138, 2005.