Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks.

The cellular response to DNA double-strand breaks (DSBs) is mobilized by the protein kinase ATM, which phosphorylates key players in the DNA damage response (DDR) network. A major question is how ATM controls DSB repair. Optimal repair requires chromatin relaxation at damaged sites. Chromatin reorganization is coupled to dynamic alterations in histone posttranslational modifications. Here, we show that in human cells, DSBs induce monoubiquitylation of histone H2B, a modification that is associated in undamaged cells with transcription elongation. We find that this process relies on recruitment to DSB sites and ATM-dependent phosphorylation of the responsible E3 ubiquitin ligase: the RNF20-RNF40 heterodimer. H2B monoubiquitylation is required for timely recruitment of players in the two major DSB repair pathways-nonhomologous end-joining and homologous recombination repair-and optimal repair via both pathways. Our data and previous data suggest a two-stage model for chromatin decondensation that facilitates DSB repair.

Ursolic acid supplementation decreases markers of skeletal muscle damage during resistance training in resistance-trained men: a pilot study.

Ursolic acid (UA) supplementation was previously shown to improve skeletal muscle function in resistance-trained men. This study aimed to determine, using the same experimental paradigm, whether UA also has beneficial effects on exercise-induced skeletal muscle damage markers including the levels of cortisol, B-type natriuretic peptide (BNP), myoglobin, creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) in resistance-trained men. Sixteen healthy participants were randomly assigned to resistance training (RT) or RT+UA groups (n=8 per group). Participants were trained according to the RT program (60~80% of 1 repetition, 6 times/week), and the UA group was additionally given UA supplementation (450 mg/day) for 8 weeks. Blood samples were obtained before and after intervention, and cortisol, BNP, myoglobin, CK, CK-MB, and LDH levels were analyzed. Subjects who underwent RT alone showed no significant change in body composition and markers of skeletal muscle damage, whereas RT+UA group showed slightly decreased body weight and body fat percentage and slightly increased lean body mass, but without statistical significance. In addition, UA supplementation significantly decreased the BNP, CK, CK-MB, and LDH levels (p<0.05). In conclusion, UA supplementation alleviates increased skeletal muscle damage markers after RT. This finding provides evidence for a potential new therapy for resistance-trained men.

The Novel Ribonucleotide Reductase Inhibitor COH29 Inhibits DNA Repair In Vitro.

COH29 [N-(4-(3,4-dihydroxyphenyl)-5-phenylthiazol-2-yl)-3,4-dihydroxybenzamide], a novel antimetabolite drug developed at City of Hope Cancer Center, has anticancer activity that stems primarily from the inhibition of human ribonucleotide reductase (RNR). This key enzyme in deoxyribonucleotide biosynthesis is the target of established clinical agents such as hydroxyurea and gemcitabine because of its critical role in DNA replication and repair. Herein we report that BRCA-1-defective human breast cancer cells are more sensitive than wild-type BRCA-1 counterparts to COH29 in vitro and in vivo. Microarray gene expression profiling showed that COH29 reduces the expression of DNA repair pathway genes, suggesting that COH29 interferes with these pathways. It is well established that BRCA1 plays a role in DNA damage repair, especially homologous recombination (HR) repair, to maintain genome integrity. In BRCA1-defective HCC1937 breast cancer cells, COH29 induced more double-strand breaks (DSBs) and DNA-damage response than in HCC1937 + BRCA1 cells. By EJ5- and DR-green fluorescent protein (GFP) reporter assay, we found that COH29 could inhibit nonhomologous end joining (NHEJ) efficiency and that no HR activity was detected in HCC1937 cells, suggesting that repression of the NHEJ repair pathway may be involved in COH29-induced DSBs in BRCA1-deficient HCC1937 cells. Furthermore, we observed an accumulation of nuclear Rad51 foci in COH29-treated HCC1937 + BRCA1 cells, suggesting that BRCA1 plays a crucial role in repairing and recovering drug-induced DNA damage by recruiting Rad51 to damage sites. In summary, we describe here additional biologic effects of the RNR inhibitor COH29 that potentially strengthen its use as an anticancer agent.

Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells.

BACKGROUND & AIMS: Chronic oxidative stress from reactive oxygen species (ROS) produced by the mitochondria promotes hepatocarcinogenesis and tumor progression. However, the exact mechanism by which mitochondrial ROS contributes to tumor cell invasion is not known. We investigated the role of ROS modulator 1 (Romo1) in hepatocellular carcinoma (HCC) development and tumor cell invasiveness. METHODS: We performed real-time, semi-quantitative, reverse transcriptase polymerase chain reaction; invasion and luciferase assays; and immunofluorescence and immunohistochemical analyses. The formation of pulmonary metastatic nodules after tumor cell injection was tested in severe combined immunodeficient mice. We analyzed Romo1 expression in HCC cell lines and tissues (n = 95). RESULTS: Expression of Romo1 was increased in HCC cells, compared with normal human lung fibroblast cells. Exogenous expression of Romo1 in HCC cells increased their invasive activity, compared with control cells. Knockdown of Romo1 in Hep3B and Huh-7 HCC cells reduced their invasive activity in response to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Levels of Romo1 were increased compared with normal liver tissues in 63 of 95 HCC samples from patients. In HCC samples from patients, there was an inverse correlation between Romo1 overexpression and patient survival times. Increased levels of Romo1 also correlated with vascular invasion by the tumors, reduced differentiation, and larger tumor size. CONCLUSIONS: Romo1 is a biomarker of HCC progression that might be used in diagnosis. Reagents that inhibit activity of Romo1 and suppress mitochondrial ROS production, rather than eliminate up-regulated intracellular ROS, might be developed as cancer therapies.

ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair.

The cellular response to double-strand breaks (DSBs) in DNA is a complex signalling network, mobilized by the nuclear protein kinase ataxia-telangiectasia mutated (ATM), which phosphorylates many factors in the various branches of this network. A main question is how ATM regulates DSB repair. Here, we identify the DNA repair enzyme polynucleotide kinase/phosphatase (PNKP) as an ATM target. PNKP phosphorylates 5'-OH and dephosphorylates 3'-phosphate DNA ends that are formed at DSB termini caused by DNA-damaging agents, thereby regenerating legitimate ends for further processing. We establish that the ATM phosphorylation targets on human PNKP-Ser 114 and Ser 126-are crucial for cellular survival following DSB induction and for effective DSB repair, being essential for damage-induced enhancement of the activity of PNKP and its proper accumulation at the sites of DNA damage. These findings show a direct functional link between ATM and the DSB-repair machinery.

Cr-catalysed ethylene dimerization in an ionic liquid-organic solvent biphasic system with perfect 1-butene selectivity.

Cr-catalyzed ionic liquid-organic biphasic ethylene dimerization was realized with 100% 1-butene selectivity. The perfect α-olefin selectivity can be rationalized in terms of the poor solubility of the oligomerized long-chain olefins in ionic liquids, and enables the establishment of a dimerization process without any complicated and energy-intensive catalyst and byproduct separation processes.

FOXO3-dependent suppression of PD-L1 promotes anticancer immune responses via activation of natural killer cells.

Boosting anticancer immunity by blocking immune checkpoints such as the programmed death-1 (PD-1) or its ligand (PD-L1) is a breakthrough anticancer therapy. However, many cancer patients do not respond well to immune checkpoint blockades (ICBs) alone. Here we show that low-dose pharmacological immunoactivators (e.g., SN38, topotecan, sorafenib, etc.) notably downregulate PD-L1 and upregulate FOXO3 expression in various human and murine cancer cell lines. In a mouse tumor model, low-dose SN38 treatment markedly suppresses tumor growth, reduces PD-L1 expression, and enhances FOXO3 expression in primary tumor specimens. SN38 therapy engages the tumor-infiltrating mouse NK1.1/CD49b/NKG2D-positive natural killer (NK) cells to attack tumor cells by inducing mouse IFN-γ and granzyme-B secretion in the tumor microenvironment (TME) in vivo. SN38 treatment also promotes tumor cell apoptosis in the TME. SN38 treatment significantly decreases STAT3-pY705 and IL-6 protein levels; FOXO3 is essential for SN38-mediated PD-L1 downregulation. Collectively, these findings may contribute to future translational or clinical investigations tackling difficult-to-treat cancers with immune-activating medicines or combined with ICB immunotherapy.

Sensitizing tumors to anti-PD-1 therapy by promoting NK and CD8+ T cells via pharmacological activation of FOXO3.

BACKGROUND: Stimulating antitumor immunity by blocking programmed death-1 (PD-1) or its ligand (programmed death-ligand 1 (PD-L1) is a promising antitumor therapy. However, numerous patients respond poorly to PD-1/PD-L1 blockade. Unresponsiveness to immune-checkpoint blockade (ICB) can cast significant challenges to the therapeutic options for patients with hard-to-treat tumors. There is an unmet clinical need to establish new therapeutic approaches for mitigating ICB unresponsiveness in patients. In this study, we investigated the efficacy and role of low-dose antineoplastic agent SN-38 or metformin in sensitizing unresponsive tumors to respond to ICB therapy. METHODS: We assessed the significant pathological relationships between PD-L1 and FOXO3 expression and between PD-L1 and c-Myc or STAT3 expression in patients with various tumors. We determined the efficacy of low-dose SN-38 or metformin in sensitizing unresponsive tumors to respond to anti-PD-1 therapy in a syngeneic tumor system. We deciphered novel therapeutic mechanisms underlying the SN-38 and anti-PD-1 therapy-mediated engagement of natural killer (NK) or CD8+ T cells to infiltrate tumors and boost antitumor immunity. RESULTS: We showed that PD-L1 protein level was inversely associated with FOXO3 protein level in patients with ovarian, breast, and hepatocellular tumors. Low-dose SN-38 or metformin abrogated PD-L1 protein expression, promoted FOXO3 protein level, and significantly increased the animal survival rate in syngeneic mouse tumor models. SN-38 or metformin sensitized unresponsive tumors responding to anti-PD-1 therapy by engaging NK or CD8+ T cells to infiltrate the tumor microenvironment (TME) and secret interferon-γ and granzyme B to kill tumors. SN-38 suppressed the levels of c-Myc and STAT3 proteins, which controlled PD-L1 expression. FOXO3 was essential for SN38-mediated PD-L1 suppression. The expression of PD-L1 was compellingly linked to that of c-Myc or STAT3 in patients with the indicated tumors. CONCLUSION: We show that SN-38 or metformin can boost antitumor immunity in the TME by inhibiting c-Myc and STAT3 through FOXO3 activation. These results may provide novel insight into ameliorating patient response to overarching immunotherapy for tumors.

Microfluidic synthesis of a cell adhesive Janus polyurethane microfiber.

We present a simple synthetic approach for the preparation of cell attachable Janus polyurethane (PU) microfibers in a microfluidic system. The synthesis was performed by using laminar flows of multiple streams with spontaneous formation of carbon dioxide bubbles resulting in an asymmetrically porous PU microfiber. The fabricated asymmetric microfiber (Janus microfiber) provides two distinctive properties: one is a porous region to promote the cellular adhesion and the other is a nonporous region rendering the mechanical strength of the scaffold. The Janus microfibers show dramatic improvement of cell adhesion, proliferation, and viability over a culture period. Cells cultured on the fibers easily bridged gaps between microfibers by joining together to form a cell sheet. The maximum distance between fibers that fibroblasts bridged is approximately 200 microm over 15 days. The Janus microfiber can be used for not only an alternative 2D cell culture plate but also as a novel 3D scaffold for tissue engineering without any need for elegant surface modification for enhancing cell adhesions.

Novel one-pot route to monodisperse thermosensitive hollow microcapsules in a microfluidic system.

We present a simple one-pot synthetic approach for the preparation of monodisperse thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) microcapsules in a microfluidic system. Based on the mechanism of shear force-driven break-off, aqueous droplets of monomer solution are continuously generated in an immiscible continuous phase containing photoinitiators. Under UV irradiation, activated initiators are diffused into the interface between the continuous phase and the aqueous droplets, which trigger polymerization of NIPAM monomers. The PNIPAM microcapsules produced are hollow microcapsules with a thin shell membrane, high monodispersity, and fast response to environmental temperature. In addition, the size of microcapsules produced can be manipulated by the flow rate of the continuous phase or aqueous phase and different concentrations of surfactant to control interfacial tension between continuous phase and aqueous phase. Furthermore, the versatility of this approach enables the preparation of monodisperse microcapsules having the capability to encapsulate various materials such as proteins and nanoparticles under mild conditions. The in situ microfluidic synthetic method provides a novel approach for the preparation of monodisperse hollow microcapsules via a one-pot route.

Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesis.

INTRODUCTION: Estrogen receptors (ERs) play key roles in breast cancer development and influence treatment outcome in breast cancer patients. Identification of molecules that regulate ER function may facilitate development of breast cancer treatment strategies. The forkhead box class O (FOXO) transcription factor FOXO3a has been suggested to function as a tumor suppressor in breast cancer. Using protein-protein interaction screening, we found that FOXO3a interacted with ER-alpha and ER-beta proteins in the human breast carcinoma cell line MCF-7, suggesting that there exists a crosstalk between the FOXO3a and ER signaling pathways in estrogen-dependent breast cancer cells. METHODS: The interaction between FOXO3a and ER was investigated by using co-immunoprecipitation and immunoblotting assays. Inhibition of ER-alpha and ER-beta transactivation activity by FOXO was determined by luciferase reporter assays. Cell proliferation in culture was evaluated by counting cell numbers. Tumorigenesis was assessed in athymic mice that were injected with MCF-7 cell lines over-expressing FOXO3a. Protein expression levels of cyclin-dependent kinase inhibitors, cyclins, ERs, FOXM1, and the proteins encoded by ER-regulated genes in MCF-7 cell lines and breast tumors were examined by immunoblotting analysis and immunohistochemical staining. RESULTS: We found that FOXO3a interacted with ER-alpha and ER-beta proteins and inhibited 17beta-estradiol (E2)-dependent, ER-regulated transcriptional activities. Consistent with these observations, expression of FOXO3a in the ER-positive MCF-7 cells decreased the expression of several ER-regulated genes, some of which play important roles in cell proliferation. Moreover, we found that FOXO3a upregulated the expression of the cyclin-dependent kinase inhibitors p21Cip1, p27Kip1, and p57Kip2. These findings suggest that FOXO3a induces cell growth arrest to effect tumor suppression. FOXO3a repressed the growth and survival of MCF-7 cells in cell culture. In an orthotopic breast cancer xenograft model in athymic mice, over-expression of FOXO3a in MCF-7 cells suppressed their E2-induced tumorigenesis, whereas knockdown of FOXO3a in MCF-7 resulted in the E2-independent growth. CONCLUSION: Functional interaction between FOXO3a and ER plays a critical role in suppressing estrogen-dependent breast cancer cell growth and tumorigenesis in vivo. This suggests that agents that activate FOXO3a may be novel therapeutic agents that can inhibit and prevent tumor proliferation and development in breast cancer.

A critical role for Romo1-derived ROS in cell proliferation.

Low levels of endogenous reactive oxygen species (ROS) originating from NADPH oxidase have been implicated in various signaling pathways induced by growth factors and mediated by cytokines. However, the main source of ROS is known to be the mitochondria, and increased levels of ROS from the mitochondria have been observed in many cancer cells. Thus far, the mechanism of ROS production in cancer cell proliferation in the mitochondria is not well-understood. We recently identified a novel protein, ROS modulator 1 (Romo1), and reported that increased expression of Romo1-triggered ROS production in the mitochondria. The experiments conducted in the present study showed that Romo1-derived ROS were indispensable for the proliferation of both normal and cancer cells. Furthermore, whilst cell growth was inhibited by blocking the ERK pathway in cells transfected with siRNA directed against Romo1, the cell growth was recovered by addition of exogenous hydrogen peroxide. The results of this study suggest that Romo1-induced ROS may play an important role in redox signaling in cancer cells.

Mitochondrial ribosomal protein L41 suppresses cell growth in association with p53 and p27Kip1.

The p53 protein arrests the cell cycle at the G1 phase when stabilized by the interaction between ribosomal proteins and HDM2 under growth-inhibitory conditions. Meanwhile, p53, when translocated to the mitochondria in response to cell death signals, induces apoptosis via transcription-independent mechanisms. In this report, we demonstrate that the mitochondrial ribosomal protein L41 (MRPL41) enhances p53 stability and contributes to p53-induced apoptosis in response to growth-inhibitory conditions such as actinomycin D treatment and serum starvation. An analysis of MRPL41 expression in paired normal and tumor tissues revealed lower expression in tumor tissue. Ectopic MRPL41 expression resulted in inhibition of the growth of cancer cells in tissue culture and tumor growth in nude mice. We discovered that MRPL41 protein is localized in the mitochondria, stabilizes the p53 protein, and enhances its translocation to the mitochondria, thereby inducing apoptosis. Interestingly, in the absence of p53, MRPL41 stabilizes the p27(Kip1) protein and arrests the cell cycle at the G1 phase. These results suggest that MRPL41 plays an important role in p53-induced mitochondrion-dependent apoptosis and MRPL41 exerts a tumor-suppressive effect in association with p53 and p27 (Kip1).

Systemic administration of minocycline inhibits formalin-induced inflammatory pain in rat.

It has been demonstrated that spinal microglial activation is involved in formalin-induced pain and that minocycline, an inhibitor of microglial activation, attenuate behavioral hypersensitivity in neuropathic pain models. We investigated whether minocycline could have any anti-nociceptive effect on inflammatory pain, after intraperitonial administration of minocycline, 1 h before formalin (5%, 50 microl) injection into the plantar surface of rat hindpaw. Minocycline (15, 30, and 45 mg/kg) significantly decreased formalin-induced nociceptive behavior during phase II, but not during phase I. The enhancement in the number of c-Fos-positive cells in the L4-5 spinal dorsal horn (DH) and the magnitude of paw edema induced by formalin injection during phase II were significantly reduced by minocycline. Minocycline inhibited synaptic currents of substantia gelatinosa (SG) neurons in the spinal DH, whereas membrane electrical properties of dorsal root ganglion neurons were not affected by minocycline. Analysis with OX-42 antibody revealed the inhibitory effect of minocycline on microglial activation 3 days after formalin injection. These results demonstrate the anti-nociceptive effect of minocycline on formalin-induced inflammatory pain. In addition to the well-known inhibitory action of minocycline on microglial activation, the anti-edematous action in peripheral tissue, as well as the inhibition of synaptic transmission in SG neurons, is likely to be associated with the anti-nociceptive effect of minocycline.

Microfluidic preparation of a highly active and stable catalyst by high performance of encapsulation of polyvinylpyrrolidone (PVP)-Pt nanoparticles in microcapsules.

The encapsulation of active metals in microcapsules would be highly advantageous in maintaining or improving the reaction performance of an array of widely used chemical reactions. However, conventional methods suffer from low uniformity, complicated fabrication steps, sintering, leaching, decline of catalytic activity, and/or poor reusability. Here, we report an efficient microfluidic approach to encapsulate Pt nanoparticle stabilized by polyvinylpyrrolidone (PVP) in photocurable double-emulsion droplets with semipermeable thin shells. The encapsulated catalysts are prepared by the in situ photopolymerization of a double emulsion. The rapid and exquisite microfluidics-based fabrication process successfully generates monodisperse microcapsules without loss of the PVP-Pt nanoparticles, which is the first demonstration of the microfluidic encapsulation of active metal with promising catalytic activity. Specifically, compared to quasi-homogeneous catalysis of PVP-Pt nanoparticles for 4-nitrophenol hydrogenation, the encapsulated PVP-Pt nanoparticles demonstrate excellent catalytic activity, a leaching-proof nature, and high reusability under the same reaction conditions. We envision that the approach described here may be an example of elegant catalyst design to efficiently overcome difficult problems in active-metal encapsulation and to dramatically enhance catalytic activity by taking advantage of the unique aspects of microfluidic methods.

Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo.

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. Lacking effective therapeutic options hinders treatment of TNBC. Here, we show that bepridil (BPD) and trifluoperazine (TFP), which are FDA-approved drugs for treatment of schizophrenia and angina respectively, inhibit Akt-pS473 phosphorylation and promote FOXO3 nuclear localization and activation in TNBC cells. BPD and TFP inhibit survival and proliferation in TNBC cells and suppress the growth of TNBC tumors, whereas silencing FOXO3 reduces the BPD- and TFP-mediated suppression of survival in TNBC cells. While BPD and TFP decrease the expression of oncogenic c-Myc, KLF5, and dopamine receptor DRD2 in TNBC cells, silencing FOXO3 diminishes BPD- and TFP-mediated repression of the expression of these proteins in TNBC cells. Since c-Myc, KLF5, and DRD2 have been suggested to increase cancer stem cell-like populations in various tumors, reducing these proteins in response to BPD and TFP suggests a novel FOXO3-dependent mechanism underlying BPD- and TFP-induced apoptosis in TNBC cells.

N'-(phenyl-pyridin-2-yl-methylene)-hydrazine carbodithioic acid methyl ester enhances radiation-induced cell death by targeting Bcl-2 against human lung carcinoma cells.

To develop a new radiosensitizer, we screened a chemical library and selected one chemical reagent, N'-(phenyl-pyridin-2-yl-methylene)-hydrazine carbodithioic acid methyl ester (PHCM), which was already known to have antifungal and antimicrobial properties. PHCM enhanced radiation-induced cell death and its mean calculated dose enhancement ratio was 1.17. PHCM was found to induce the phosphorylation of p38 mitogen-activated protein kinase, and combined treatment with PHCM and radiation down-regulated Bcl-2. In a xenograft assay, the combined PHCM and radiation group showed 39.3 days of growth delay versus the control in terms of tumor growth. The enhancement factor of this combined treatment was determined to be 4.02.

Effects of Low-Dose Bisphenol A on DNA Damage and Proliferation of Breast Cells: The Role of c-Myc.

BACKGROUND: Humans are exposed to low-dose bisphenol A (BPA) through plastic consumer products and dental sealants containing BPA. Although a number of studies have investigated the mammary gland effects after high-dose BPA exposure, the study findings differ. Furthermore, there has been a lack of mechanistic studies. OBJECTIVE: The objective of this study was to investigate the effect and the mechanism of low-dose BPA in mammary gland cells. METHODS: We evaluated DNA damage following BPA exposure using the comet assay and immunofluorescence staining, and used cell counting and three-dimensional cultures to evaluate effects on proliferation. We examined the expressions of markers of DNA damage and cell-cycle regulators by immunoblotting and performed siRNA-mediated gene silencing to determine the role of c-Myc in regulating BPA's effects. RESULTS: Low-dose BPA significantly promoted DNA damage, up-regulated c-Myc and other cell-cycle regulatory proteins, and induced proliferation in parallel in estrogen receptor-α (ERα)-negative mammary cells. Silencing c-Myc diminished these BPA-induced cellular events, suggesting that c-Myc is essential for regulating effects of BPA on DNA damage and proliferation in mammary cells. CONCLUSIONS: Low-dose BPA exerted c-Myc-dependent genotoxic and mitogenic effects on ERα-negative mammary cells. These findings provide significant evidence of adverse effects of low-dose BPA on mammary cells.

Synergistic effect of peroxiredoxin II antisense on cisplatin-induced cell death.

Peroxiredoxin II (Prx II) is known not only to protect cells from oxidative damage caused by hydrogen peroxide (H202), but also to endow cancer cells with resistance to both H202 and cisplatin and to grant them radioresistance. In this study, we examined whether Prx II antisense could enhance cisplatin-induced cell death. When gastric cancer cells were transfected with various concentrations of Prx II antisense plasmid, pPrxII/AS, and then treated with the same concentrations of cisplatin, Prx II antisense enhanced cisplatin-induced cell death. The combination index (CI) at all doses of the combination was below 1, indicating that Prx II antisense sensitized cisplatin-induced cell death. This synergism was also observed in the cells transfected with a Prx II antisense oligomer. Our present results, therefore, suggest that Prx II antisense would be a very good sensitizer for cisplatin, and that Prx II as a target for chemosensitizers constitutes a promising avenue for future research.

Dendritic chiral auxiliaries on silica: a new heterogeneous catalyst for enantioselective addition of diethylzinc to benzaldehyde.

This article reports the first work on the use of silica supported dendritic chiral auxiliaries for the enantioselective addition of diethylzinc to benzaldehyde: the control of dendrimer propagation on the silica surface is of prime importance to obtain enhanced conversion, selectivity, and enantioselectivity.