Structure-guided engineering of Pseudomonas dacunhael-aspartate β-decarboxylase for l-homophenylalanine synthesis.

Structure-guided engineering of Pseudomonas dacunhael-aspartate β-decarboxylase (AspBDC) resulted in a double mutant (R37A/T382G) with remarkable 15 400-fold improvement in specific activity reaching 216 mU mg, towards the target substrate 3(R)-benzyl-l-aspartate. A novel strategy for enzymatic synthesis of l-homophenylalanine was developed by using the variant as a biocatalyst affording 75% product yield within 12 h. Our results underscore the potential of engineered AspBDC for the biocatalytic synthesis of pharmaceutically relevant and value added unnatural l-amino acids.

Andrographolide-loaded silk fibroin nanoparticles.

Andrographolide (AP) is a diterpenoid separated from with a wide spectrum of biological activities including anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemic. However, its poor water solubility and instability result in lower bioavailability, which seriously limit its pharmacological function. In this study, the attempt to use regenerated silk fibroin (RSF) as a drug-carrier to encapsulate AP was reported.

Anordrin Eliminates Tamoxifen Side Effects without Changing Its Antitumor Activity.

Tamoxifen is administered for estrogen receptor positive (ER) breast cancers, but it can induce uterine endometrial cancer and non-alcoholic fatty liver disease (NAFLD). Importantly, ten years of tamoxifen treatment has greater protective effect against ER breast cancer than five years of such treatment. Tamoxifen was also approved by the FDA as a chemopreventive agent for those deemed at high risk for the development of breast cancer.

Diastereodivergent Catalytic Asymmetric Michael Addition of 2-Oxindoles to α,β-Unsaturated Ketones by Chiral Diamine Catalysts.

A diastereodivergent catalytic asymmetric Michael addition of 2-oxindoles to α,β-unsaturated ketones has been successfully developed with two complementary chiral diamine catalysts, affording chiral 3,3-disubstituted oxindoles with two adjacent chiral centers. Diastereodivergence has been realized through modifying substrates and utilizing different catalysts. Either anti-or syn-configured products possessing vicinal quaternary and tertiary stereogenic centers were produced with high enantioselectivities.

Construction of the isocopalane skeleton: application of a desulfinylative 1,7-hydrogen atom transfer strategy.

Two attractive chirons, aldehyde 6 and chloride 7, exhibiting functionalized ent-spongiane-type tricyclic skeletons (ABC ring system), have been constructed and their absolute configurations have been studied by NMR spectroscopy and confirmed by single-crystal X-ray diffraction. Both of these chirons are derived from commercially available andrographolide in good yield. Aldehyde 6 is obtained through a novel K2 S2 O8 -catalyzed aquatic ring-closing reaction of allylic sodium sulfonate and intramolecular 1,7-hydrogen atom transfer process.

A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-β-blocker precursors.

Microtuning of the enzyme active pocket has led to a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots. This study represents a breakthrough in protein engineering of epoxide hydrolases and resulted in enhanced activity toward bulky substrates.

Discovery of N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement.

The present study discovers multiple N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement. The current [2,3] rearrangement of epoxy or acetal O-substituents converting to diol or alcohol N-substituents can be promoted by silica gel or by diluted hydrochloric acid, which is distinct from previously reported [2,3] rearrangements. Some of the derivatives displayed comparable or even stronger cytotoxicity than sorafenib and vemurafenib on HCT116 colon carcinoma and A375 melanoma cell lines.

Overman rearrangement and Pomeranz-Fritsch reaction for the synthesis of benzoazepinoisoquinolones to discover novel antitumor agents.

The B-ring of Benzoazepinoisoquinolones 1a-b was successfully constructed by Pomeranz-Fritsch reaction. The key intermediates 5a-b could be transformed from 9a-b via Overman rearrangement. The bioassay showed that 11 compounds are more active than sorafenib (IC₅₀ = 7.

Highly selective, naked-eye and fluorescent "off-on" probe for detection of histidine/histidine-rich proteins and its application in living cell imaging.

A highly selective colorimetric and fluorescence enhanced probe S1 (M2@Cu) for histidine and histidine-rich proteins has been developed. In neutral aqueous ethanol solution, probe S1 can selectively detect histidine out of twenty DNA encoded amino acids by showing a color change from brownish red to light green, and with a fluorescence enhancement up to 99-fold at 537 nm, simultaneously.

Versatile trifunctional chemosensor of rhodamine derivative for Zn2+, Cu2+ and His/Cys in aqueous solution and living cells.

On the basis of rhodamine, a versatile trifunctional chemosensor RP has been synthesized. It can selectively and sensitively recognize Cu(2+) and Zn(2+) in different solutions. Based on the zinc-containing [RP@Zn(2+)] complex, it shows highly selective recognition for His/Cys.

Synthesis of the scalarane sesterterpenoid 16-deacetoxy-12-epi-scalarafuranacetate.

The marine natural product 16-deacetoxy-12-epi-scalarafuranacetate, isolated from Spongua officinalis , was synthesized in 18 linear steps, starting from (-)-sclareol, with high stereoselectivity and an overall yield of 6.1%. The intermediate 16-deacetoxy-12-epi-scalarafuran could be easily transformed into a series of natural scalarane sesterterpenoids in a few steps.

Modulating the selectivity of near-IR fluorescent probes toward various metal ions by judicious choice of aqueous buffer solutions.

The near-infrared fluorescent probes S1 and S2 based on the BODIPY skeleton were designed and synthesized. They showed different selectivity in various aqueous buffer solutions. Judicious choice of buffer solutions can modulate the selectivity of fluorescent sensors toward a specific metal ion.

Apoptosis induction of ZBB-006, a novel synthetic diterpenoid, in the human hepatocellular carcinoma cell line HepG2 in vitro and in vivo.

Diterpenes, present in many medicinal plants, have been the focus of continuous studies for the development of new anticancer agents. ZBB-006 is a new synthetic diterpenoid derivative which exhibited significant anti-proliferation activity against various cancer cell lines in our previous study. Here, we investigated the antitumor effect of ZBB-006 and its potential mechanisms in the human hepatocellular carcinoma cell line HepG2, both in vitro and in vivo.

Isotope-coded, iodoacetamide-based reagent to determine individual cysteine pK(a) values by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Cysteine reactivity in enzymes is imparted to a large extent by the stabilization of the deprotonated form of the reduced cysteine (i.e., the thiolate) within the active site.

Synthesis of chemical probes to map sulfenic acid modifications on proteins.

Cysteine sulfenic acids in proteins can be identified by their ability to form adducts with dimedone, but this reagent imparts no spectral or affinity tag for subsequent analyses of such tagged proteins. Given its similar reactivity toward cysteine sulfenic acids, 1,3-cyclohexadione was synthetically modified to an alcohol derivative and linked to fluorophores based on isatoic acid and 7-methoxycoumarin. The resulting compounds retain full reactivity and specificity toward cysteine sulfenic acids in proteins, allowing for incorporation of the fluorescent label into the protein and "tagging" it based on its sulfenic acid redox state.

A molecular target for suppression of the evolution of antibiotic resistance: inhibition of the Escherichia coli RecA protein by N(6)-(1-naphthyl)-ADP.

We report that N(6)-(1-naphthyl)-ADP inhibits the Escherichia coli RecA protein in vitro. A novel rapid screen identified it as a potent inhibitor of RecA nucleoprotein filament formation, and further characterization established it as an ATP-competitive inhibitor of RecA-catalyzed ATP hydrolysis. This and other inhibitors of RecA activities represent a new approach for understanding the molecular targets and pathways involved in the evolution of antibiotic resistance in bacteria.

Nitroxyl (HNO) release from new functionalized N-hydroxyurea-derived acyl nitroso-9,10-dimethylanthracene cycloadducts.

A thermal retro-Diels-Alder decomposition of N-hydroxyurea-derived acyl nitroso compounds and 9,10-dimethylanthracene cycloadducts followed by acyl nitroso compound hydrolysis produces nitrous oxide, evidence for the formation of nitroxyl, the one-electron reduced form of nitric oxide that has drawn considerable attention for its potential roles in biological systems. EPR and NMR spectroscopy provide further evidence for nitroxyl formation and kinetic information, respectively. Such compounds may prove to be useful alternative nitroxyl donors.

Direct observation of an acyl nitroso species in solution by time-resolved IR spectrocopy.

Benzoyl nitroside (5) was generated in solution by laser photolysis of 3,5-diphenyl-1,2,4-oxadiazole-4-oxide (4) and studied by time-resolved infrared spectroscopy. The second-order rate constants for reaction of 5 with diethylamine and 1,3-cyclohexadiene were determined to be (1.3 +/- 0.

Studies on mimicry of naturally occurring annonaceous acetogenins: non-THF analogues leading to remarkable selective cytotoxicity against human tumor cells.

A class of structurally simplified analogues of the naturally occurring annonaceous acetogenins were developed, amongst which some non-THF analogues showed remarkable cytotoxicities against tumor cell lines, as well as good selectivity between human tumor cells and normal cells. The synthetic routes were significantly shortened because of the removal of the chiral centers bearing the THF rings on the natural templates. This simplification also provides access to the parallel synthesis of these mimics by a combinatorial strategy.

Straightforward synthesis of two pairs of enantiomeric butenolides 3-tetradecyl- and 3-hexadecyl-5-methyl-2(5H)-furanone.

Based on the synthetic method of optically active 3-alkyl-5-methyl-2(5H)-furanones from lactic acid, two pairs of chiral butenolides 3-tetradecyl- and 3-hexadecyl-5-methyl-2(5H)-furanone have been straightforwardly synthesized from methyl stearate and methyl palmitate respectively by aldol condensation with (R)- or (S)-O-tetrahydropyranyl lactal prepared from corresponding ethyl lactate and beta-elimination.

Mimicry of annonaceous acetogenins: enantioselective synthesis of a (4R)-hydroxy analogue having potent antitumor activity.

The (4R)-hydroxylated analogues of annonaceous acetogenin mimicking compound 2 were designed and synthesized structurally on the basis of the naturally occurring annonaceous acetogenin bullatacin, which was discovered as a typical member of the novel family of polyketides with potent cytotoxicity, antitumoral, and other biological activities. The preliminary screenings show that the IC(50) values of 2 were 1.6 x 10(-3) and 8 x 10(-2) microg/mL against HT-29 and HCT-8, respectively.