Rational Design of a Two‐Photon Fluorogenic Probe for Visualizing Monoamine Oxidase A Activity in Human Glioma Tissues

Abstract

Monoamine oxidases have two functionally distinct but structurally similar isoforms (MAO-A and MAO-B). The ability to differentiate them by using fluorescence detection/ imaging technology is of significant biological relevance,b ut highly challenging with available chemical tools.H erein, we report the first MAO-A-specific two-photon fluorogenic probe (F1), capable of selective imaging of endogenous MAO-A enzymatic activities from av ariety of biological samples, including MAO-A-expressing neuronal SY-SY5Y cells,t he brain of tumor-bearing mice and human Glioma tissues by using two-photon fluorescence microscopy( TPFM) with minimal cytotoxicity.

Two-Photon Fluorescent Probes for Detecting Enzyme Activities in Live Tissues

“…MAOs are divided into two forms, MAO A and B based on their substrate and inhibitor selectivity . The overexpression of MAOs is observed in cardiovascular and neurodegenerative diseases. , The two-photon probes been developed continuously to map MAOs activities in biological systems. − Recently, Yao and Huang group developed MAO-A specific TP fluorescent probe 13 based on their previous studies during development of MAO-B probe . The nonfluorescent 13 consists of N -alkylated tetrahydropyridine as the MAO-A recognition unit undergoes enzyme catalyzed oxidization, followed by the rapid conversion to highly fluorogenic 13-MAO-A (Figure a).…”

“…CL-pretreatment (MAOs inhibitor) was done where indicated. (c) Average fluorescence intensity profiles of reconstructed tissues image in b. Reproduced with permission from ref . Copyright 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…82−84 Recently, Yao and Huang group developed MAO-A specific TP fluorescent probe 13 based on their previous studies during development of MAO-B probe. 84 The nonfluorescent 13 consists of N-alkylated tetrahydropyridine as the MAO-A recognition unit undergoes enzyme catalyzed oxidization, followed by the rapid conversion to highly fluorogenic 13-MAO-A (Figure 8a). Comprehensive studies on probe 13 in biological samples showed impressive selectivity and specificity toward the MAO-A enzyme.…”

Merging liquid crystalline self-assembly and linear optical properties of merocyanines via tailored donor units

“…Merocyanines are a unique class of donor-acceptor dyes, where the terminal donor and acceptor moieties are connected via a p-conjugating unit. [1][2][3][4] Prominent examples are rhodols 1 5,6 spiropyrane-derived merocyanines 2, 3, [7][8][9][10][11] indolenine-indandione derivatives 4 12,13 and barbiturates 5, 6 (Scheme 1), [14][15][16] which have been successfully utilized for a variety of applications, most notably chemosensors, [7][8][9][10][11] biological imaging, biomolecule targeting, redox probes, 5,6 fluorescence resonance enhanced transfer (FRET)-based applications, 8 p-type organic semiconductors in organic electronics and photovoltaics, [12][13][14]16 non-linear optical switches, 10 chiral amplification, 15 multidimensional electronic spectroscopy to monitor photochemical reactions, 9 photoswitching, 11,17,18 photosensitizers for photodynamic therapy 19 and dyes showing aggregation-induced emission (AIEgens). 20 However, surprisingly little work has been devoted to merocyanines showing liquid crystalline selfassembly.…”

“…Fig. 6 DSC curves of (a) Mal-1-C(8)F(8), (b) O-1-C(6)F(6), (c) Mal-1-C(6)F(6) and (d) Mal-2-C(8)F(6). Shown in each case is the second heating/cooling cycle (bottom: heating; top: cooling).…”