Structural modification of 2-phenylquinoline-4-carboxylic acid containing SIRT3 inhibitors for the cancer differentiation therapy.

Inhibition of SIRT3 exhibited potency in triggering leukemic cell differentiation. In discovery of potent SIRT3 inhibitors for cancer differentiation therapy, structural modification was performed on the previously developed lead compound P6. A total of 33 compounds were designed and synthesized. In the enzyme inhibitory assay, several molecules S18, S26, S27 and T5 showed potent SIRT3 inhibitory activity with IC50 value of 0.53, 1.86, 5.06, and 2.88 µM, respectively. Moreover, the tested compounds exhibited SIRT3 inhibitory selectivity over SIRT1 and SIRT2. Compounds S27 and T5 were potent in inhibition the growth of MM1.S and RPMI-8226 cells in the in vitro antiproliferative test. Significantly, representative compounds, especially S27 and T5, promoted differentiation of tested MM cells in the cellular morphological evaluation, accompanied by increasing the expression of differentiation antigen CD49e and human immunoglobulin light chain lambda and kappa. Additionally, molecule S18 without antiproliferative potency itself, showed significant inhibitory activity against growth factor IL-6 induced RPMI-8226 cell proliferation. Collectively, potent SIRT3 selective inhibitors with MM cell differentiation potency were developed for further discovery of anticancer drugs.

Glutathione-Sensitive Photosensitizer-Drug Conjugates Target the Mitochondria to Overcome Multi-Drug Resistance in Cancer.

Multi-drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH-sensitive photosensitizer-drug conjugates (CyR-SS-L) are designed and synthesized. CyR-SS-L localized in the mitochondria then is cleaved into CyR-SG and SG-L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR-SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG-L part is used for chemotherapy. CyR-SS-L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR-SS-L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.

Differentiation of imatinib -resistant chronic myeloid leukemia cells with BCR-ABL-T315I mutation induced by Jiyuan Oridonin A.

Chronic myeloid leukemia (CML) results from BCR-ABL oncogene, which blocks CML cells differentiation and protects these cells from apoptosis. T315I mutated BCR-ABL is the main cause of the resistance mediated by imatinib and second generation BCR-ABL inhibitor. CML with the T315I mutation has been considered to have poor prognosis. Here, we determined the effect of Jiyuan oridonin A (JOA), an ent-kaurene diterpenoid compound, on the differentiation blockade in imatinib-sensitive, particularly, imatinib-resistant CML cells with BCR-ABL-T315I mutation by cell proliferation assay, apoptosis analysis, cell differentiation analysis, cell cycle analysis and colony formation assay. We also investigated the possible molecular mechanism by mRNA sequencing, qRT-PCR and Western blotting. We found that JOA at lower concentration significantly inhibited the proliferation of CML cells expressing mutant BCR-ABL (T315I mutation included) and wild-type BCR-ABL, which was due to that JOA induced the cell differentiation and the cell cycle arrest at G0/G1 phase. Interestingly, JOA possessed stronger anti-leukemia activity than its analogues such as OGP46 and Oridonin, which has been investigated extensively. Mechanistically, the cell differentiation mediated by JOA may be originated from the inhibition of BCR-ABL/c-MYC signaling in CML cells expressing wild-type BCR-ABL and BCR-ABL-T315I. JOA displayed the activity of inhibiting the BCR-ABL and promoted differentiation of not only imatinib -sensitive but also imatinib -resistant cells with BCR-ABL mutation, which could become a potent lead compound to overcome the imatinib -resistant induced by inhibitors of BCR-ABL tyrosine kinase in CML therapy.

Jiyuan oridonin A induces differentiation of acute myeloid leukemia cells including leukemic stem-like cells.

Acute myeloid leukemia (AML) is an aggressive form of hematological neoplasia characterized by failure of myeloid differentiation. AML is a leading cause of death from leukemia. Cytarabine chemotherapy resistance is a major source of refractory/relapsed AML. A major obstacle to the successful treatment of AML results from residual disease maintained by leukemic stem cells (LSCs), which are mostly resistant to conventional chemotherapy. Here, we determined the effect of a natural compound, Jiyuan oridonin A (JOA), on the differentiation blockade in the M2 subtype [particularly t (8;21)] of AML cells, M3 subtype of AML cells (APL cells), and leukemic stem-like cells both in vitro and in vivo. We found that JOA induced cell differentiation and suppressed the colony formation capacity in various AML cell lines (Kasumi-1, KG-1, MUTZ-8, NB4, and HL-60) without eliciting apoptosis. The mechanism of JOA-induced cell differentiation depends on the specificity of cell type. JOA mediated the differentiation of Kasumi-1 cells by activating the hematopoietic cell lineage signaling pathway, while inhibition of c-MYC was involved in the JOA-induced differentiation of NB4 cells. Moreover, JOA was identified to target leukemic stem-like cells by induced cell differentiation in vivo. These findings demonstrated that JOA could inhibit the proliferation of M2 and M3 subtypes of AML cells and leukemic stem-like cells by overcoming the differentiation blockade, which may offer a novel therapeutic strategy for AML to overcome relapse and drug resistance in patients with AML. Our findings highlight the possibility of using compounds like JOA as a promising differentiation-induced agent for the treatment of AML.

Discovery and SAR analysis of phenylbenzo[d][1,3]dioxole-based proprotein convertase subtilisin/kexin type 9 inhibitors.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel therapeutic target for the development of cholesterol-lowering drugs. In the discovery of PCSK9/LDLR (low-density lipoprotein receptor) protein-protein interaction (PPI) impairing small molecules, a total of 47 phenylbenzo[d][1,3] dioxole-based compounds were designed and synthesised. The result revealed that the 4-chlorobenzyl substitution in the amino group is important for the PPI disrupting activity. In the hepatocyte-based functional tests, active compounds such as A12, B1, B3, B4 and B14, restored the LDLR levels on the surface of hepatic HepG2 cells and increased extracellular LDL uptake in the presence of PCSK9. It is notable that molecule B14 exhibited good performance in all the evaluations. Collectively, novel structures targeting PCSK9/LDLR PPI have been developed with hypolipidemic potential. Further structural modification of derived active compounds is promising in the discovery of lead compounds with improved activity for the treatment of hyperlipidaemia-related disorders.

Simultaneous self-supply of H2O2 and GSH-depleted intracellular oxidative stress for enhanced photodynamic/photothermal/chemodynamic therapy.

Herein, we designed a new nanoplatform for combined PDT/PTT/CDT through simultaneously self-supplying H2O2 and depleting GSH using one single laser irradiation. The nanoplatform was capable of generating multiple reactive oxygen species (ROS), such as 1O2, O2-˙ and ˙OH, resulting in cell death. Moreover, the nanoplatform demonstrated low dark toxicity, high phototoxicity and better biosafety. In vivo animal experiments showed that the tumor growth was efficiently inhibited.

Discovery and SAR analysis of 5-chloro-4-((substituted phenyl)amino)pyrimidine bearing histone deacetylase inhibitors.

Histone deacetylases (HDACs) are validated targets for the development of anticancer drugs in epigenetics. In the discovery of novel HDAC inhibitors with anticancer potency, the 5-chloro-4-((substituted phenyl)amino)pyrimidine fragment is assembled as a cap group into the structure of HDAC inhibitors. The SAR revealed that presence of small groups (such as methoxy substitution) is beneficial for the HDAC inhibitory activity. In the enzyme inhibitory selectivity test, compound L20 exhibited class I selectivity with IC50 values of 0.684 µM (selectivity index of >1462), 2.548 µM (selectivity index of >392), and 0.217 µM (selectivity index of >4608) against HDAC1, HDAC2 and HDAC3 compared with potency against HDAC6 (IC50 value of >1000 µM), respectively. In the antiproliferative assay, compound L20 showed both hematological and solid cancer inhibitory activities. In the flow cytometry, L20 promoted G0/G1 phase cell cycle arrest and apoptosis of K562 cells.

Discovery of Novel Tetrahydro-ß-carboline Containing Aminopeptidase N Inhibitors as Cancer Chemosensitizers.

Aminopeptidase N (APN, CD13) is closely associated with the development and progression of cancer. Previous studies suggested APN as a biomarker for cancer stem cells. APN inhibitors have been intensively evaluated as chemosensitizers for cancer treatments. In the present study, tetrahydro-ß-carboline scaffold was introduced to the structure of APN inhibitors. The synthesized compounds showed potent enzyme inhibitory activities compared with Bestatin, an approved APN inhibitor, in cell-based enzymatic assay. In combination with chemotherapeutic drugs, representative APN inhibitor molecules D12, D14 and D16 significantly improved the antiproliferative potency of anticancer drugs in the in vitro tests. Further mechanistic studies revealed that the anticancer effects of these drug combinations are correlated with decreased APN expression, increased ROS level, and induction of cell apoptosis. The spheroid-formation assay and colony-formation assay results showed effectiveness of Paclitaxel-APN inhibitor combination against breast cancer stem cell growth. The combined drug treatment led to reduced mRNA expression of OCT-4, SOX-2 and Nanog in the cancer stem cells tested, suggesting the reduced stemness of the cells. In the in vivo study, the selected APN inhibitors, especially D12, exhibited improved anticancer activity in combination with Paclitaxel compared with Bestatin. Collectively, potent APN inhibitors were discovered, which could be used as lead compounds for tumor chemo-sensitization and cancer stem cell-based therapies.

Association between tumor morphology and dosimetric parameters of organs at risk after intensity-modulated radiotherapy in esophagus cancer.

PURPOSE: We explored the effects of geometrical topological properties of tumors such as tumor length and "axial cross-sectional area (ACSA)" of tumors (planning target volume [PTV] volume /PTV length) on the dosimetric parameters of organs at risk (lung and heart) in patients with esophagus cancer (EPC) treated by way of intensity-modulated radiation therapy (IMRT), so as to provide a guideline for the dosimetric limitation for organs at risk in IMRT treatment. METHODS: A retrospective analysis was done on 103 cases of patients with EPC who were treated by IMRT from November 2010 to August 2019, in which PTV-G stood for the externally expanded planning target volume (PTV) of the gross tumor volume (GTV) and PTV-C for the externally expanded volume of the clinical target volume (CTV). A linear regression model was employed to analyze the several pairs of correlation: the 1st one between the relative length of tumors (PTV length/lung length) and pulmonary dose-volume parameters, the 2nd one between ACSA of tumors and pulmonary dose-volume parameters, the 3rd one between PTV length and the dosimetric parameters of the heart, and the last one between ACSA of tumors and the dosimetric parameters of the heart. RESULTS: (i) There was a strong positive correlation between the relative length of tumors (PTV length/lung length) and V5 (p < 0.001, r = 0.73), and V10 (p < 0.001, r = 0.66) of the lung. There was a moderate positive correlation between the relative length of tumors and V30 (p < 0.001, r = 0.44) of the lung, and a weak positive correlation between the relative length of tumors and V20 (p < 0.001, r = 0.39) of the lung. (ii) There was a strong positive correlation between ACSA of tumors (PTV volume/PTV length) and V30 (p < 0.001, r = 0.67) of the lung, a moderate positive correlation between ACSA of tumors and V20 (p <0.001, r = 0.51) of the lung, and a weak positive correlation between ACSA of tumors and V10 (p = 0.019, r = 0.23) of the lung, yet there was not an obvious correlation between ACSA of tumors and V5 p > 0.05) of the lung. (iii) There was a moderate positive correlation between PTV length and V40 (p < 0.001, r = 0.58), and Dmean (p < 0.001, r = 0.52) of the heart, yet there was no obvious correlation between ACSA of tumors and Dmean and V40 of the heart (p > 0.05). CONCLUSIONS: (i) Compared with the high-dose region of the lung, the relative length of tumors (PTV length/lung length) has a greater impact on the low-dose region of the lung. The linear regression equation of scatter plot showed that when the relative length of tumors increased by 0.1, the lung dose-volume parameters of V5 , V10 , V20 , and V30 increased by approximately 5.37%, 3.59%, 1.05%, and 1.08%, respectively. When PTV length increased by 1 cm, Dmean and V40 of the heart increased by approximately 153.6 cGy and 2.03%, respectively. (ii) Compared with the low-dose region of the lung, the value of ACSA of tumors (PTV volume/PTV length) has a greater impact on the high-dose region of the lung. However, the value of ACSA of tumors has no significant effect on the dosimetric parameters of the heart (Dmean and V40 ). The linear regression equation of scatter plot showed that when ACSA of tumors increased by 10 cm2 , the lung dose-volume parameters of V10 , V20, and V30 increased by approximately 3.11%, 3.37%, and 4.01%, respectively.

A simultaneously GSH-depleted bimetallic Cu(ii) complex for enhanced chemodynamic cancer therapy.

A bimetallic Cu(ii) complex as a novel antitumor chemodynamic therapy agent with glutathione (GSH) depletion properties is successfully synthesized and well characterized. In tumor cells, the Cu2+ ions of the complex are reduced to Cu+ ions by GSH and then catalyzed by the overexpressed H2O2 to generate highly cytotoxic hydroxyl radicals (˙OH) that kill cancer cells. The complex is quickly taken up by cancer cells and distributed in multiple organelles including mitochondria and the nucleus. The complex demonstrates good cytotoxicity toward various cancer cell lines. However, its toxicity toward normal cells is significantly lower than that toward cancer cells due to the limited expression of H2O2. In addition, the complex could arrest the cell cycle of the G0/G1 phase, thereby inducing apoptosis rather than necrosis.

A synergistic bactericidal effect of low-frequency and low-intensity ultrasound combined with levofloxacin-loaded PLGA nanoparticles on M. smegmatis in macrophages.

PURPOSE: Tuberculosis (TB) is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb), which often parasites in macrophages. This study is performed to investigate the bactericidal effect and underlying mechanisms of low-frequency and low-intensity ultrasound (LFLIU) combined with levofloxacin-loaded PLGA nanoparticles (LEV-NPs) on M. smegmatis (a surrogate of Mtb) in macrophages. METHODS AND RESULTS: The LEV-NPs were prepared using a double emulsification method. The average diameter, zeta potential, polydispersity index, morphology, and drug release efficiency in vitro of the LEV-NPs were investigated. M. smegmatis in macrophages was treated using the LEV-NPs combined with 42 kHz ultrasound irradiation at an intensity of 0.13 W/cm2 for 10 min. The results showed that ultrasound significantly promoted the phagocytosis of nanoparticles by macrophages (P < 0.05). In addition, further ultrasound combined with the LEV-NPs promoted the production of reactive oxygen species (ROS) in macrophage, and the apoptosis rate of the macrophages was significantly higher than that of the control (P < 0.05). The transmission electronic microscope showed that the cell wall of M. smegmatis was ruptured, the cell structure was incomplete, and the bacteria received severe damage in the ultrasound combined with the LEV-NPs group. Activity assays showed that ultrasound combined with the LEV-NPs exhibited a tenfold higher antibacterial activity against M. smegmatis residing inside macrophages compared with the free drug. CONCLUSION: These data demonstrated that ultrasound combined with LEV-NPs has great potential as a therapeutic agent for TB.

Identification of Human IDO1 Enzyme Activity by Using Genetically Encoded Nitrotyrosine.

Human indoleamine 2,3-dioxygenase 1 (IDO1) has become an increasingly valuable target for cancer immunotherapy because it promotes immune escape by tumor cells. To date, the function of post-translational modifications (PTMs) on IDO1 has not been fully elucidated. Among the many forms of PTMs, it has been identified that three tyrosine sites (Y15, Y345, and Y353) on IDO1 are nitrated and play important roles in catalytic function. Herein, by genetically encoding 3-nitro-l-tyrosine into the tyrosine nitration sites of IDO1, the homogeneous and native nitrated IDO1 have been obtained. It is found that the nitration of different tyrosine sites has different effects on the IDO1 structure and enzyme activity. Nitration at position Y15 has a negligible effect, but nitration at Y345 or Y353 decreases the enzyme activity, especially Y353. Furthermore, these results demonstrate that the regulation of the catalytic function caused by tyrosine nitration is related to perturbation of the protein structure and heme-binding disruption.

The marine-derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα.

Recent studies have demonstrated that commercially available lipid-lowering drugs cause various side effects; therefore, searching for anti-hyperlipidaemic compounds with lower toxicity is a research hotspot. This study was designed to investigate whether the marine-derived compound, 5-hydroxy-3-methoxy-5-methyl-4-butylfuran-2(5H)-one, has an anti-hyperlipidaemic activity, and the potential underlying mechanism in vitro. Results showed that the furanone had weaker cytotoxicity compared to positive control drugs. In RAW 264.7 cells, the furanone significantly lowered ox-LDL-induced lipid accumulation (~50%), and its triglyceride (TG)-lowering effect was greater than that of liver X receptor (LXR) agonist T0901317. In addition, it significantly elevated the protein levels of peroxisome proliferator-activated receptors (PPARα) and ATP-binding cassette (ABC) transporters, which could be partially inhibited by LXR antagonists, GSK2033 and SR9243. In HepG2 cells, it significantly decreased oleic acid-induced lipid accumulation, enhanced the protein levels of low-density lipoprotein receptor (LDLR), ABCG5, ABCG8 and PPARα, and reduced the expression of sterol regulatory element-binding protein 2 (~32%). PPARα antagonists, GW6471 and MK886, could significantly inhibit the furanone-induced lipid-lowering effect. Furthermore, the furanone showed a significantly lower activity on the activation of the expression of lipogenic genes compared to T0901317. Taken together, the furanone exhibited a weak cytotoxicity but had powerful TC- and TG-lowering effects most likely through targeting LXRα and PPARα, respectively. These findings indicate that the furanone has a potential application for the treatment of dyslipidaemia.

A novel Mn-Cu bimetallic complex for enhanced chemodynamic therapy with simultaneous glutathione depletion.

A bimetallic complex, containing Mn(ii) and Cu(ii) moieties, was synthesized for chemodynamic therapy (CDT) of cancer. The complex was capable of generating a hydroxyl radical (˙OH) via a Fenton-like reaction involving a Mn complex, and simultaneously depleting glutathione via a Cu complex induced oxidative reaction, thereby enhancing the efficiency of CDT.

Ultrasonic exposure parameters screening in permeability of mycobacterium smegmatis cytoderm induced by cavitation based on artificial neural network identification.

The low intensity ultrasound has been adopted by researchers to enhance the bactericidal effect against bacteria in vitro and in vivo. Although the mechanism is not completely understood, one dominant opinion is that the permeability increases because of acoustic cavitation. However, the relationship between ultrasonic exposure parameters and cavitation effects is not definitely addressed. In this paper, by establishing a modified artificial neural network (ANN) model between ultrasonic parameters and cavitation effects, the cavitation effects can be predicted and inversely the direction for choosing parameters can be given despite of different ultrasonic systems. Compared with the generic model, the computational results obtained by modified model are more close to experimental results with low calculation cost. It means that as an efficient solution, the validity of the new model has been proved. Although the research is of preliminary stage, the new method may have great value and significance because of reducing the experimental expense. The next step of this research is to explore an optimization method to obtain the most suitable parameters based on this identification model. We hope it can give a guideline for future applications in ultrasonic therapy.

Dataset of the infrared spectrometry, gas chromatography-mass spectrometry analysis and nuclear magnetic resonance spectroscopy of the polysaccharides from C. militaris.

The data presented in this article describe characteristics of the polysaccharides, designated as CM1 and CMS, isolated from the fruiting body of C. militaris. Fourier transform infrared spectrometry analysis was used to identify the basic characteristics of the polysaccharides and the completeness of methylation. Gas chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy were carried out to reveal the glycosidic linkages of CM1 and CMS. Further interpretation and discussion could be found at our research article entitled "Structural characterisation and cholesterol efflux improving capacity of the novel polysaccharides from Cordyceps militaris" (Hu et al., 2019; https://doi.org/10.1016/j.ijbiomac.2019.03.078) [1].

Stilbenoids and cannabinoids from the leaves of Cannabis sativa f. sativa with potential reverse cholesterol transport activity.

Three new stilbenoids (1-3) and 16 known stilbenoids (4-6) and cannabinoids (7-19) were isolated from the leaves of hemp (Cannabis sativa L.). The structures of the three new compounds were identified as α,α'-dihydro-3',4,5'-trihydroxy-4'-methoxy-3-isopentenylstilbene (HM1), α,α'-dihydro-3,4',5-trihydroxy-4-methoxy-2,6-diisopentenylstilbene (HM2), and α,α'-dihydro-3',4,5'-trihydroxy-4'-methoxy-2',3-diisopentenylstilbene (HM3) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known α,α'-dihydro-3,4',5-trihydroxy-4,5'-diisopentenylstilbene (5) and combretastatin B-2 (6) were isolated for the first time from C. sativa f. sativa. These isolated compounds exhibited cytotoxic effects on human cancer cells via inhibiting the proliferation of cancer cells and inducing cell death. Among them, compounds 4, 5, 10, 12, 13, 15, and 19 displayed broad-spectrum cytotoxicity, and 1, 7, and 11 displayed selectivity in inhibition efficiency on MCF-7 and A549 cells, which suppressed the proliferation of cancer cells significantly by inducing cell death. The effects of compounds 1-3 on improving reverse cholesterol transport (RCT) were evaluated by isotope-tracing and western blotting. Results showed that the three stilbenoids showed a cytotoxicity above 1.0 mg L-1, especially that of HM3. They could improve [3H]-cholesterol efflux from Raw 264.7 macrophages to high density lipoproteins by enhancing the protein expression of ABCG1 and SR-B1, and HM1 and HM2 showed a significant difference compared with fenofibrate at 1.0 mg L-1. The three stilbenoids could also significantly improve the protein expression of ABCA1. Further study on HepG2 cells indicated that they improve the protein expression of LDLR, SR-B1 and CYP7A1, especially that of HM1 and HM3. However, they showed no significant effect on PCSK9. The above results indicated that these stilbenoids may elevate the transfer of cholesterol to hepatocytes by improving the protein expression of SR-B1 and LDLR, and the synthesis of bile acid by increasing the protein expression of CYP7A1. In conclusion, HM1 showed lower cytotoxicity and higher activity in improving the RCT-related protein expression. Our study suggests that it may be explored as a novel lipid-lowering drug and as a beneficial ingredient in health functional foods and pharmaceuticals.

Cleavage of a carbon-fluorine bond by an engineered cysteine dioxygenase.

Cysteine dioxygenase (CDO) plays an essential role in sulfur metabolism by regulating homeostatic levels of cysteine. Human CDO contains a post-translationally generated Cys93-Tyr157 cross-linked cofactor. Here, we investigated this Cys-Tyr cross-linking by incorporating unnatural tyrosines in place of Tyr157 via a genetic method. The catalytically active variants were obtained with a thioether bond between Cys93 and the halogen-substituted Tyr157, and we determined the crystal structures of both wild-type and engineered CDO variants in the purely uncross-linked form and with a mature cofactor. Along with mass spectrometry and 19F NMR, these data indicated that the enzyme could catalyze oxidative C-F or C-Cl bond cleavage, resulting in a substantial conformational change of both Cys93 and Tyr157 during cofactor assembly. These findings provide insights into the mechanism of Cys-Tyr cofactor biogenesis and may aid the development of bioinspired aromatic carbon-halogen bond activation.

A genetically encoded 19F NMR probe for lysine acetylation.

Advances in acetylated protein-protein/DNA interactions depend on the development of a novel NMR (nuclear magnetic resonance) probe to study the conformational changes of acetylated proteins. However, the method for detecting the acetylated protein conformation is underdeveloped. Herein, an acetyllysine mimic has been exploited for detecting the conformational changes of acetylated p53-protein/DNA interactions by genetic code expansion and 19F NMR. This 19F NMR probe shows high structural similarity to acetyllysine and could not be deacetylated by sirtuin deacetylase in vitro/vivo. Moreover, acetylation of p53 K164 is reported to be deacetylated by SIRT2 for the first time.

Sodium borohydride-nickel chloride hexahydrate in EtOH/PEG-400 as an efficient and recyclable catalytic system for the reduction of alkenes.

An efficient, safe and one-pot convenient catalytic system has been developed for the reduction of alkenes using NaBH4-NiCl2·6H2O in EtOH/PEG-400 under mild conditions. In this catalytic system, a variety of alkenes (including trisubstituted alkene α-pinene) were well reduced and the Ni catalyst could be recycled.