Glycosidase-targeting small molecules for biological and therapeutic applications.

Glycosidases are ubiquitous enzymes that catalyze the hydrolysis of glycosidic linkages in oligosaccharides and glycoconjugates. These enzymes play a vital role in a wide variety of biological events, such as digestion of nutritional carbohydrates, lysosomal catabolism of glycoconjugates, and posttranslational modifications of glycoproteins. Abnormal glycosidase activities are associated with a variety of diseases, particularly cancer and lysosomal storage disorders. Owing to the physiological and pathological significance of glycosidases, the development of small molecules that target these enzymes is an active area in glycoscience and medicinal chemistry. Research efforts carried out thus far have led to the discovery of numerous glycosidase-targeting small molecules that have been utilized to elucidate biological processes as well as to develop effective chemotherapeutic agents. In this review, we describe the results of research studies reported since 2018, giving particular emphasis to the use of fluorescent probes for detection and imaging of glycosidases, activity-based probes for covalent labelling of these enzymes, glycosidase inhibitors, and glycosidase-activatable prodrugs.

Glycan microarrays from construction to applications.

Through their specific interactions with proteins, cellular glycans play key roles in a wide range of physiological and pathological processes. One of the main goals of research in the areas of glycobiology and glycomedicine is to understand glycan-protein interactions at the molecular level. Over the past two decades, glycan microarrays have become powerful tools for the rapid evaluation of interactions between glycans and proteins. In this review, we briefly describe methods used for the preparation of glycan probes and the construction of glycan microarrays. Next, we highlight applications of glycan microarrays to rapid profiling of glycan-binding patterns of plant, animal and pathogenic lectins, as well as other proteins. Finally, we discuss other important uses of glycan microarrays, including the rapid analysis of substrate specificities of carbohydrate-active enzymes, the quantitative determination of glycan-protein interactions, discovering high-affinity or selective ligands for lectins, and identifying functional glycans within cells. We anticipate that this review will encourage researchers to employ glycan microarrays in diverse glycan-related studies.

Near-infrared (NIR) fluorescence-emitting small organic molecules for cancer imaging and therapy.

Near-infrared (NIR) fluorophores have unique features that endow them with several advantages over conventional shorter wavelength emitting dyes. As a result, they have been widely utilized as fluorescence and photoacoustic imaging agents, as well as photodynamic and photothermal therapeutic agents. However, non-targeting NIR fluorescence-emitting organic molecules have the drawback of low selectivity toward tumors, which potentially results in severe side effects caused by damage to normal tissues. Thus, the development of NIR fluorophore-based substances that target tumors is a highly active area in medicinal chemistry research. Research efforts carried out thus far have led to the development of a number of NIR fluorophore-based, tumor imaging and therapeutic agents. The discussion in this review focuses on the results of research reported in the 2012-2021 period, giving particular emphasis to studies of NIR small organic dye-based imaging and therapeutic agents that are designed utilizing cancer-selective strategies.

Multivalent glycans for biological and biomedical applications.

Recognition of glycans by proteins plays a crucial role in a variety of physiological processes in cells and living organisms. In addition, interactions of glycans with proteins are involved in the development of diverse diseases, such as pathogen infection, inflammation and tumor metastasis. It is well-known that multivalent glycans bind to proteins much more strongly than do their monomeric counterparts. Owing to this property, numerous multivalent glycans have been utilized to elucidate glycan-mediated biological processes and to discover glycan-based biomedical agents. In this review, we discuss recent advances (2014-2020) made in the development and biological and biomedical applications of synthetic multivalent glycans, including neoglycopeptides, neoglycoproteins, glycodendrimers, glycopolymers, glyconanoparticles and glycoliposomes. We hope this review assists researchers in the design and development of novel multivalent glycans with predictable activities.

A fluorogenic probe targeting two spatially separated enzymes for selective imaging of cancer cells.

We describe a fluorogenic probe BocLys(Ac)-AB-FC targeting both histone deacetylases (HDACs) and cathepsin L, which are overexpressed in spatially separated subcellular organelles of cancer cells. The results show that this fluorogenic probe can be used for selective cancer cell imaging without interference arising from normal cells.

New fluorescent metal-ion detection using a paper-based sensor strip containing tethered rhodamine carbon nanodots.

A strip of tethered rhodamine carbon nanodots (C-dots) was designed for selective detection of Al(3+) ion using a Förster resonance energy transfer (FRET)-based ratiometric sensing mechanism. The probe consisted of rhodamine B moieties immobilized on the surface of water-soluble C-dots. Upon exposure to Al(3+), the rhodamine moieties showed a much enhanced emission intensity via energy transfer from the C-dots under excitation at their absorption wavelength. The detection mechanism was related to the Al(3+)-induced ring-opening of rhodamine on C-dots through the chelation of the rhodamine 6G moiety with Al(3+), leading to a spectral overlap of the absorption of C-dots (donor) and the emission of ring-opened rhodamine (acceptor). In addition, a paper-based sensor strip containing the tethered rhodamine C-dots was prepared for practical, versatile applications of Al(3+) sensing. The paper-based sensor could detect Al(3+) over other metal ions efficiently, even from a mixture of metal ions, with increased emission intensity at long-wavelength emission via FRET. Sensing based on FRET of C-dots is color-tunable, can be recognized with a naked eye, and may provide a new platform for specific metal-ion sensing.

Simultaneous detection and removal of radioisotopes with modified alginate beads containing an azo-based probe using RGB coordinates.

We prepared alginate beads that were modified with an azo-based probe molecule to monitor simultaneously the removal (by alginate) and probing (by the azo-probe molecule) of radioisotopes such as cobalt, strontium, and cesium ions. As an azo-probe molecule, Basic Orange 2 (BO2) was immobilized to the alginate bead. The BO2 in aqueous solution exhibited a slight red shift in absorption with a change in color from orange to dark orange upon addition of cobalt and strontium ions. In contrast, the color of BO2 did not change upon exposure to cesium ions. Thus, the covalently embedded BO2 in alginate beads could adsorb cobalt and strontium ions resulting in recognizable color change of the beads, which was induced by the formation of a complex between BO2 and metal ions. The color changes of the beads in the presence of metal ions were determined quantitatively using RGB color coordinate values. In addition to effectively removing metal ions, the colorimetric coordinate method provides a convenient and simple sensing technique for naked-eye metal ion detection.