Bioluminescent imaging (BLI) has been widely applicable in the imaging of process envisioned in life sciences. As the most conventional technique for BLI, the firefly luciferin-luciferase system is ...exceptionally functional
in vitro
and
in vivo
. The state-of-the-art strategy in such a system is to cage the luciferin, in which free luciferin is conjugated with distinctive functional groups, thus accommodating an impressive toolkit for exploring various biological processes, such as monitoring enzymes activity, detecting bioactive small molecules, evaluating the properties of molecular transporters,
etc.
This review article summarizes the rational design of caged luciferins towards diverse biotargets, as well as their applications in bioluminescent imaging. It should be emphasized that these caged luciferins can stretch out the applications of bioluminescence imaging and shed light upon understanding the pathogenesis of various diseases.
This review article summarizes the rational design of caged firefly luciferins towards diverse biotargets, as well as their applications in bioluminescent imaging.
Local polarity can affect the physical or chemical behaviors of surrounding molecules, especially in organisms. Cell polarity is the ultimate feedback of cellular status and regulation mechanisms. ...Hence, the abnormal alteration of polarity in organisms is closely linked with functional disorders and many diseases. It is incredibly significant to monitor and detect local polarity to explain the biological processes and diagnoses of some diseases. Because of their
in vivo
safe and real-time monitoring, several polarity-sensitive fluorophores and fluorescent probes have gradually emerged and been used in modern research. This review summarizes the fluorescence properties and applications of several representative polarity-sensitive fluorescent probes.
Polarity-sensitive fluorophores can change their fluorescence properties in response to the polarity of local surroundings, such as excitation and emission wavelength (
λ
ex
, and
λ
em
), fluorescence quantum yield (
Φ
f
), fluorescence lifetime and so on.
Full text
Available for:
IJS, KILJ, NUK, UL, UM, UPUK
As the cardinal support of innumerable biological processes, biomacromolecules such as proteins, nucleic acids and polysaccharides are of importance to living systems. The key to understanding ...biological processes is to realize the role of these biomacromolecules in thte localization, distribution, conformation and interaction with other molecules. With the current development and adaptation of fluorescent technologies in biomedical and pharmaceutical fields, the fluorescence imaging (FLI) approach of using small-molecule fluorescent probes is becoming an up-to-the-minute method for the detection and monitoring of these imperative biomolecules in life sciences. However, conventional small-molecule fluorescent probes may provide undesirable results because of their intrinsic deficiencies such as low signal-to-noise ratio (SNR) and false-positive errors. Recently, small-molecule fluorescent probes with a photoinduced electron transfer (PET) "on/off" switch for biomacromolecules have been thoroughly considered. When recognized by the biomacromolecules, these probes turn on/off the PET switch and change the fluorescence intensity to present a high SNR result. It should be emphasized that these PET-based fluorescent probes could be advantageous for understanding the pathogenesis of various diseases caused by abnormal expression of biomacromolecules. The discussion of this successful strategy involved in this review will be a valuable guide for the further development of new PET-based small-molecule fluorescent probes for biomacromolecules.
This review article summarizes the advances in fluorescent probes on the basis of the photoinduced electron transfer (PET) mechanism towards diverse biomacromolecule targets, as well as their applications in fluorescent imaging.
Molecular docking, which is the indispensable emphasis in predicting binding conformations and energies of ligands to receptors, constructs the high-throughput virtual screening available. So far, ...increasingly numerous molecular docking programs have been released, and among them, AutoDock 4.2 is a widely used docking program with exceptional accuracy. It has heretofore been substantiated that the calculation of partial charge is very fundamental for the accurate conformation search and binding energy estimation. However, no systematic comparison of the significances of electrostatic potentials on docking accuracy of AutoDock 4.2 has been determined. In this paper, nine different charge-assigning methods, including AM1-BCC, Del-Re, formal, Gasteiger–Hückel, Gasteiger–Marsili, Hückel, Merck molecular force field (MMFF), and Pullman, as well as the ab initio Hartree–Fock charge, were sufficiently explored for their molecular docking performance by using AutoDock4.2. The results clearly demonstrated that the empirical Gasteiger–Hückel charge is the most applicable in virtual screening for large database; meanwhile, the semiempirical AM1-BCC charge is practicable in lead compound optimization as well as accurate virtual screening for small databases.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Hypochlorous (HOCl) acid is generated as a defense tool in the immune system and plays a vital role in killing a wide range of pathogens. There is therefore great interest in developing fluorescent ...probes that can endogenously respond to the change in concentration of HOCl in vivo. To address this challenge, we here present a rapidly responding fluorescent probe RO610 to image endogenous HOCl in living mice. The development of RO610 was based on a novel water-soluble and pH-independent fluorescent xanthene dye, 2'-formylrhodol ROA, which exhibits highly selective and sensitive responses to HOCl/ClO
over other reactive species. Moreover, adding a little more than 5 equiv. of ClO
to the solution of RO610 resulted in a clearly observable fluorescence enhancement (48-fold) within 30 s. Based on these properties, RO610 was used to detect ClO
in A549 cells without interference by other oxidants. It was applied for the imaging of endogenous HOCl in living nude mice with satisfactory results.
Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here we propose a self-delivering one-component ...new-chemical-entity nanomedicine (ONN) strategy to improve cancer therapy through incorporation of the self-assembly principle into drug design. A lysosomotropic detergent (MSDH) and an autophagy inhibitor (Lys05) are hybridised to develop bisaminoquinoline derivatives that can intrinsically form nanoassemblies. The selected BAQ12 and BAQ13 ONNs are highly effective in inducing lysosomal disruption, lysosomal dysfunction and autophagy blockade and exhibit 30-fold higher antiproliferative activity than hydroxychloroquine used in clinical trials. These single-drug nanoparticles demonstrate excellent pharmacokinetic and toxicological profiles and dramatic antitumour efficacy in vivo. In addition, they are able to encapsulate and deliver additional drugs to tumour sites and are thus promising agents for autophagy inhibition-based combination therapy. Given their transdisciplinary advantages, these BAQ ONNs have enormous potential to improve cancer therapy.
Glioblastoma (GBM) is among the most common and malignant types of primary brain tumors in adults, with a dismal prognosis. Although alkylating agents such as temozolomide are widely applied as the ...first-line treatment for GBM, they often cause chemoresistance and remain ineffective with recurrent GBM. Alternative therapeutics against GBM are urgently needed in the clinic. We report herein the discovery of a class of inhibitors (YZ129 and its derivatives) of the calcineurin-NFAT pathway that exhibited potent anti-tumor activity against GBM. YZ129-induced GBM cell-cycle arrest at the G2/M phase promoted apoptosis and inhibited tumor cell proliferation and migration. At the molecular level, YZ129 directly engaged HSP90 to antagonize its chaperoning effect on calcineurin to abrogate NFAT nuclear translocation, and also suppressed other proto-oncogenic pathways including hypoxia, glycolysis, and the PI3K/AKT/mTOR signaling axis. Our data highlight the potential for targeting the cancer-promoting HSP90 chaperone network to treat GBM.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To enhance the efficiency of firefly luciferase/luciferin bioluminescence imaging, a series of N-cycloalkylaminoluciferins (cyaLucs) were developed by introducing lipophilic N-cycloalkylated ...substitutions. The experimental results demonstrate that these cyaLucs are effective substrates for native firefly luciferase (Fluc) and can produce elevated bioluminescent signals in vitro, in cellulo, and in vivo. It should be noted that, in animal studies, N-cyclobutylaminoluciferin (cybLuc) at 10 μM (0.1 mL), which is 0.01% of the standard dose of d-luciferin (dLuc) used in mouse imaging, can radiate 20-fold more bioluminescent light than d-luciferin (dLuc) or aminoluciferin (aLuc) at the same concentration. Longer in vivo emission imaging using cybLuc suggests that it can be used for long-time observation. Regarding the mechanism of cybLuc, our cocrystal structure data from firefly luciferase with oxidized cybLuc suggested that oxidized cybLuc fits into the same pocket as oxyluciferin. Most interestingly, our results demonstrate that the sensitivity of cybLuc in brain tumor imaging contributes to its extended application in deep tissues.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
PDF
