Abstract

One of the great challenges in the post-genome era is to clarify the biological significance of intracellular molecules directly in living cells. If we can visualize a molecule in action, it is possible to acquire biological information, which is unavailable if we deal with cell homogenates. One possible approach is to design and synthesize sensor molecules that can convert biological information to chemical reactions that are easily monitored. For this purpose, fluorescence sensor molecules for intracellular messengers have been developed and successfully applied to living cells.Ratiometric measurement is a technique to reduce artifacts by minimizing the influence of extraneous factors on the fluorescence of a sensor molecule. FRET is one mechanism that is applicable for ratiometric measurement. We have designed two FRET sensor molecules, based on changing donor-acceptor distance and changing overlap integral. Protein tyrosine phosphatase activity was successfully monitored by designed sensor. Design, synthesis and neurological application of Zn2+ specific sensor molecules are also introduced.

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