Nanosized high relaxivity MR contrast agents by conjugation to virus capsids

AEI 61

Ankona Datta, ankona_datta@berkeley.edu1, Jacob M. Hooker, jmhooker@berkeley.edu1, Mauro Botta2, Matthew B. Francis, francis@cchem.berkeley.edu1, and Kenneth N. Raymond, raymond@socrates.berkeley.edu1. (1) Department of Chemistry, University of California at Berkeley, Berkeley, CA 94720, (2) Dipartimento di Scienze e Tecnologie Avanzate, Universita del Piemonte Orientale "Amedeo Avogadro", Alessandria, Italy, Alessandria, Italy
Virus capsids can provide stable scaffolds for development of nano-sized macromolecular MR contrast agents. Attachment of small-molecule contrast agents to virus capsids can lead to higher relaxivities and thus greater contrast enhancement due to the slow molecular tumbling of the macromolecule. Gd(III)-Hydroxypyridonate-based complexes were covalently conjugated either to the interior or exterior of empty MS2 virus capsids. The internal conjugates were obtained by covalent conjugation to tyrosines in the interior of the capsids, while the externally-modified capsids were obtained by conjugation to lysines. The resultant nano-sized contrast agents exhibit four fold higher relaxivities compared to the small-molecule Gd-complex with maximum values as high as 41.6 mM-1s-1 at 30 MHz for the internally-modified capsids. The relaxometric properties of these conjugates were probed by measuring the NMRD profiles and temperature dependence of the relaxivities. The details of the conjugation strategy, relaxometric studies, and effects of local versus global motions of the conjugates on relaxivity, will be presented.
 

Academic Employment Initiative
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Academic Employment Initiative

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007