Novel NMR Platform for Detecting Gene Transfection: Synthesis and Evaluation of Fluorinated Phenyl -D
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文摘
Gene therapy holds great promise for the treatment of diverse diseases, but widespread implementationis hindered by difficulties in assessing the success of transfection. The development of noninvasivereporter techniques based on appropriate molecules and imaging modalities may help to assay geneexpression. Fluorophenyl-ages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-D-galactopyranosides provide a novel class of NMR active molecules, whichare highly responsive to the action of ages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-galactosidase (ages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-gal), the product of the lacZ gene. The reportermolecules are stable in solution and with respect to wild-type cells, but the enzyme causes liberationof the aglycon, a fluorophenol, accompanied by distinct color formation and a 19F NMR chemical shiftof 5-10 ppm, depending on pH. Synthetic strategy, experimental methods, and molecular and 19FNMR characteristics are reported for a series of molecules in solution, blood, and tumor cells. Thisclass of molecules presents a new strategy for assaying gene expression with a highly versatilemolecular structural platform.

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