Fluorophore-Nanogoldparticle Based Optical Breast Cancer Locator. Final Report July 1, 2008-June 30, 2010

摘要

We report synthetic routes for modifying cypate, an indocyanine green fluorophore, with custom thiol-terminated peptide and poly(ethylene glycol) (PEG) substrates. The peptide amino acid sequence serves as a recognition element for the enzyme urokinase plasminogen activator. In collaboration with Dr. Kang (partnering award W81XWH-08-1-0460), peptide, PEG and related spacer conjugates of cypate were attached to nanogold particles for evaluation of their fluorescence properties. We also describe the synthesis of a cypate bis(aldehyde) analog. We developed a new synthetic route to aminooxy- and thiol-terminated hydrophobichydrophilic diblock spacers for tethering the cypate bis(aldehyde) to nanogold particles via oximation couplings. In conjunction with a novel aminooxy blocking group (used to modulate cypate polarity), the oximation methodology enabled evaluation of diblock spacer length on cypate fluorescence emission. Finally, we report a synthesis of a tamoxifen-aldehyde for convenient attachment to aminooxy spacers as a means for targeting the nanogold particles.