Highlights► Comparing biofuel crops is exceedingly difficult using conventional measurement methods. ► The PETRO approach quantitatively compares biological matter in terms of energy and carbon. ► Tracking carbon flux from air to liquid fuel compares all biofuel crop yields on a common basis. ► Reporting energy yields (GJ ha−1 y−1) and carbon flux (MgC ha−1 y−1) enables regional comparison. 相似文献
Highlights► A wide variety of bioreporter and biosensor assays for arsenic detection exists. ► Assay detection limits are mostly in the range of 10–50 μg As per L and below. ► New focus is on reporter integration into microdevices for more optimal detection. ► A number of case studies show realistic field applicability of bioreporter assays. 相似文献
Identification of neuropsychiatric CNVs. A) Schematic of a deletion and duplication. B) Example of a locus enriched for deletions in cases. C) Number of risk CNVs implicated in published studies of neuropsychiatric disorders. The number of cases included in each study is shown on the x axis, and larger points represent studies with more control samples (see Table 1 for further details). SCZ = schizophrenia, ASD = autism spectrum disorder, ID = intellectual disability, MDD = major depressive disorder, ADHD = attention-deficit hyperactivity disorder, TS = Tourette syndrome, OCD = obsessive compulsive disorder, BD = bipolar disorder.
The apelinergic system includes a series of endogenous peptides apelin, ELABELA/TODDLER and their 7-transmembrane G-protein coupled apelin receptor (APJ, AGTRL-1, APLNR). The APJ receptor is an attractive therapeutic target because of its involvement in cardiovascular diseases and potentially other disorders including liver fibrosis, obesity, diabetes, and neuroprotection. To date, pharmacological characterization of the APJ receptor has been limited due to the lack of small molecule functional agonists or antagonists. Through focused screening we identified a drug-like small molecule agonist hit 1 with a functional EC50 value of 21.5 ± 5 μM and binding affinity (Ki) of 5.2 ± 0.5 μM. Initial structure–activity studies afforded compound 22 having a 27-fold enhancement in potency and the first sub-micromolar full agonist with an EC50 value of 800 ± 0.1 nM and Ki of 1.3 ± 0.3 μM. Preliminary SAR, synthetic methodology, and in vitro pharmacological characterization indicate this scaffold will serve as a favorable starting point for further refinement of APJ potency and selectivity.
An efficient one-pot synthetic procedure has been developed for the preparation of heteroarenyl-benzimidazoles via oxidative Csp3-H functionalization with o-phenylenediamine using I2-DMSO in open air from easily available starting materials. Based on a logical plan a spectrum of multi fundamental reactions like iodination, Kornblum oxidation and amination were brought into one-pot. By using this simple method a library of heteroarenyl-benzimidazoles derivatives (3a–t and 5a–g) and heteroarenyl-benzothiazole (3u) have been synthesized in good to excellent yield and screened for their cytotoxicity against a group of four human cancer cell lines. Among them 3h, 3q and 5b showed significant cytotoxic activities with an IC50 of 1.69, 1.62 and 2.81 µM respectively against lung cancer (A549) cell line.
A library of benzimidazole derivatives 1–20 were synthesized, and studied for their α-chymotrypsin (α-CT) inhibitory activity in vitro. Kinetics and molecular docking studies were performed to identify the type of inhibition. Compound 1 was found to be a good inhibitor of α-chymotrypsin enzyme (IC50 = 14.8 ± 0.1 μM, Ki = 16.4 μM), when compared with standard chymostatin (IC50 = 5.7 ± 0.13 μM). Compounds 2–8, 15, 17, and 18 showed significant inhibitory activities. All the inhibitors were found to be competitive inhibitors, except compound 17, which was a mixed type inhibitor. The substituents (R) in para and ortho positions of phenyl ring B, apparently played a key role in the inhibitory potential of the series. Compounds 1–20 were also studied for their cytotoxicity profile by using 3T3 mouse fibroblast cells and compounds 3, 5, 6, 8, 12–14, 16, 17, 19, and 20 were found to be cytotoxic. Molecular docking was performed on the most active members of the series in comparison to the standard compound, chymostatin, to identify the most likely binding modes. The compounds reported here can serve as templates for further studies for new inhibitors of α-chymotrypsin and other chymotrypsin-like serine proteases enzymes.
Cartoon depictions of (a) Dynamic interchange between receptor monomers, (homo, orange GPCR1, and hetero, orange GPCR1 and green GPCR2) dimers and oligomers which may be ligand regulated (orange sphere). (b) Signalling cross-talk between protomers of a dimer. Left: ligand (orange sphere) binds to one protomer and the conformational change transmitted to the second protomer results in signalling through activation of a Gα subunit (blue). Right: ligand (green sphere) binding to the second protomer may modulate signalling (large or small yellow flash).
Screening of a 65,536-member one-bead-one-compound (OBOC) combinatorial library of glycopeptide dendrimers of structure ((βGal)n + 1X8X7X6X5)2DapX4X3X2X1(β-Gal)m (βGal = β-galactosyl-thiopropionic acid, X8–1 = variable amino acids, Dap = l-2,3-diaminopropionic acid, n, m = 0, or 1 if X8 = Lys resp. X1 = Lys) for binding of Jurkat cells to the library beads in cell culture, resynthesis and testing lead to the identification of dendrimer J1 (βGal-Gly-Arg-His-Ala)2Dap-Thr-Arg-His-Asp-CysNH2 and related analogues as delivery vehicles. Cell targeting is evidenced by FACS with fluorescein conjugates such as J1F. The colchicine conjugate J1C is cytotoxic with LD50 = 1.5 μM. The β-galactoside groups are necessary for activity, as evidenced by the absence of cell-binding and cytotoxicity in the non-galactosylated, acetylated analogue AcJ1F and AcJ1C, respectively. The pentagalactosylated dendrimer J4 βGal4(Lys-Arg-His-Leu)2Dap-Thr-Tyr-His-Lys(βGal)-Cys) selectively labels Jurkat cell as the fluorescein derivative J4F, but its colchicine conjugate J4C lacks cytotoxicity. Tubulin binding assays show that the colchicine dendrimer conjugates do not bind to tubulin, implying intracellular degradation of the dendrimers releasing the active drug.
