Abstract
AbstractAbnormal expression of monoamine oxidase A (MAO−A) has been implicated in the development of human glioma, making MAO−A a promising target for therapy. Therefore, a rapid determination of MAO−A is critical for diagnosis. Through in silico screening of two‐photon fluorophores, we discovered that a derivative of N,N‐dimethyl‐naphthalenamine (pre‐mito) can effectively fit into the entrance of the MAO−A cavity. Substitutions on the N‐pyridine not only further explore the MAO−A cavity, but also enable mitochondrial targeting ability. The aminopropyl substituted molecule, CD1, showed the fastest MAO−A detection (within 20 s), high MAO−A affinity and selectivity. It was also used for in situ imaging of MAO−A in living cells, enabling a comparison of the MAO−A content in human glioma and paracancerous tissues. Our results demonstrate that optimizing the affinity binding‐based fluorogenic probes significantly improves their detection rate, providing a general approach for rapid detection probe design and optimization.
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