Discovery of a cystathionine γ-lyase (CSE) selective inhibitor targeting active-site pyridoxal 5'-phosphate (PLP) via Schiff base formation.

D,L-Propargylglycine (PAG) has been widely used as a selective inhibitor to investigate the biological functions of cystathionine γ-lyase (CSE), which catalyzes the formation of reactive sulfur species (RSS). However, PAG also inhibits other PLP (pyridoxal-5'-phosphate)-dependent enzymes such as methionine γ-lyase (MGL) and L-alanine transaminase (ALT), so highly selective CSE inhibitors are still required. Here, we performed high-throughput screening (HTS) of a large chemical library and identified oxamic hydrazide 1 as a potent inhibitor of CSE (IC = 13 ± 1 μM (mean ± S.

Recent Advances in Detection, Isolation, and Imaging Techniques for Sulfane Sulfur-Containing Biomolecules.

Hydrogen sulfide and its oxidation products are involved in many biological processes, and sulfane sulfur compounds, which contain sulfur atoms bonded to other sulfur atom(s), as found in hydropersulfides (R-S-SH), polysulfides (R-S-S-S-R), hydrogen polysulfides (HS), etc., have attracted increasing interest. To characterize their physiological and pathophysiological roles, selective detection techniques are required.

Recent advances in probe design to detect reactive sulfur species and in the chemical reactions employed for fluorescence switching.

Reactive sulfur species, including hydrogen sulfide, hydropersulfide, and polysulfide, have many roles in biological systems. For example, hydrogen sulfide is involved in the relaxation of vascular smooth muscles and mediation of neurotransmission, while sulfane sulfur, which exists in cysteine persulfide/polysulfide, and glutathione persulfide/polysulfide, is involved in physiological antioxidation and cytoprotection mechanisms. Fluorescence imaging is well suited for real-time monitoring of reactive sulfur species in living cells, and many fluorescent probes for reactive sulfur species have been reported.

A cytosolically localized far-red to near-infrared rhodamine-based fluorescent probe for calcium ions.

Ca2+ is one of the most important second messengers in cells. A far-red to near-infrared (NIR) Ca2+ fluorescent probe is useful for multi-color imaging in GFP or YFP-expressing biosamples. Here we developed a cytosolically localized far-red to NIR rhodamine-based fluorescent probe for Ca2+, CaSiR-2 AM, while rhodamine dyes are basically localized to mitochondria or lysosomes in cells.

A Fluorescent Probe for Rapid, High-Contrast Visualization of Folate-Receptor-Expressing Tumors In Vivo.

Folate receptors (FRs) are membrane proteins involved in folic acid uptake, and the alpha isoform (FR-α) is overexpressed in ovarian and endometrial cancer cells. For fluorescence imaging of FRs in vivo, the near-infrared (NIR) region (650-900 nm), in which tissue penetration is high and autofluorescence is low, is optimal, but existing NIR fluorescent probes targeting FR-α show high non-specific tissue adsorption, and require prolonged washout to visualize tumors. We have designed and synthesized a new NIR fluorescent probe, FolateSiR-1, utilizing a Si-rhodamine fluorophore having a carboxy group at the benzene moiety, coupled to a folate ligand moiety through a negatively charged tripeptide linker.

Rational Design of a Near-infrared Fluorescence Probe for Ca Based on Phosphorus-substituted Rhodamines Utilizing Photoinduced Electron Transfer.

Fluorescence imaging in the near-infrared (NIR) region (650-900 nm) is useful for bioimaging because background autofluorescence is low and tissue penetration is high in this range. In addition, NIR fluorescence is useful as a complementary color window to green and red for multicolor imaging. Here, we compared the photoinduced electron transfer (PeT)-mediated fluorescence quenching of silicon- and phosphorus-substituted rhodamines (SiRs and PRs) in order to guide the development of improved far-red to NIR fluorescent dyes.

[Development of fluorescent probes for detecting reactive sulfur species and their application to development of inhibitors for 3MST].

Hydrogen sulfide (HS) has been reported to play an important role in biological systems. More recently, sulfane sulfur (sulfur with 0 or -1 charge) molecules have been also reported to be involved in various biological phenomena such as regulation of redox signaling and antioxidant functions. Fluorescent probes are one of the important chemical tools because it is easy to use and enable the real-time detection of the target molecules in living cells and tissues.

Fluorescent Probes and Selective Inhibitors for Biological Studies of Hydrogen Sulfide- and Polysulfide-Mediated Signaling.

Significance: Hydrogen sulfide (HS) plays roles in many physiological processes, including relaxation of vascular smooth muscles, mediation of neurotransmission, inhibition of insulin signaling, and regulation of inflammation. Also, hydropersulfide (R-S-SH) and polysulfide (-S-S-S-) have recently been identified as reactive sulfur species (RSS) that regulate the bioactivities of multiple proteins via S-sulfhydration of cysteine residues (protein Cys-SSH) and show cytoprotection. Chemical tools such as fluorescent probes and selective inhibitors are needed to establish in detail the physiological roles of HS and polysulfide.