Chiral cyclic α,α-disubstituted amino acids, (3S,4S)- and (3R,4R)-1-amino-3,4-(dialkoxy)cyclopentanecarboxylic acids ((S,S)- and (R,R)-Ac(5) c(dOR) ; R: methyl, methoxymethyl), were synthesized from dimethyl L-(+)- or D-(-)-tartrate, and their homochiral homoligomers were prepared by solution-phase methods. The preferred secondary structure of the (S,S)-Ac(5) c(dOMe) hexapeptide was a left-handed (M) 3(10) helix, whereas those ...

SIRT1 is a phylogenetically conserved energy sensor. The molecular mechanisms that regulate its catalytic activity, however, are incompletely understood. Gerhart-Hines et al. (2011) have identified β-adrenergic/cAMP signaling as a regulatory input that rapidly controls SIRT1 activity and fatty acid oxidation.

The NAD(+)-dependent deacetylase SIRT1 is an evolutionarily conserved metabolic sensor of the Sirtuin family that mediates homeostatic responses to certain physiological stresses such as nutrient restriction. Previous reports have implicated fluctuations in intracellular NAD(+) concentrations as the principal regulator of SIRT1 activity. However, here we have identified a cAMP-induced phosphorylation ...

Yes, nitrenes did "N,O"! Intermolecular addition of nitrene to enecarbamates and enesulfonamides gives oxyamidated products in excellent yields of up to 98 % and with good levels of stereoselectivity. Complete regioselectivity is also observed, leading to the formation of N,O-acetals which can further react with various nucleophiles under acidic conditions (see ...

BACKGROUND: Mesona procumbens is consumed as a herbal drink and jelly-type dessert in Taiwan. The aim of this study was to determine the mechanism of anti-inflammatory activities of the aqueous extract of M. procumbens (AMP) using the λ-carrageenin (Carr)-induced mouse paw oedema model. The fingerprint chromatogram of AMP was obtained ...

A one-pot electrophilic alkoxyetherification using an olefin, a cyclic ether, a carboxylic acid, and N-bromosuccinimide has been developed. The oxygen nucleophiles, the olefinic substrates, and the cyclic ether partners can be varied to produce a wide range of alkoxyether derivatives.

A series of novel cyclic amine-substituted benzoic acid derivatives were synthesized and evaluated for their PPARα agonist activity. Strucure-activity relationship studies led to the identification of (S)-3-[3-[2-(4-chlorophenyl)-4-methylthyazole-5-carboxamido]piperidin-1-yl]benzoic acid (S)-4f (KRP-105) as a potent and high subtype-selective human PPARα agonist. (S)-4f showed excellent PK profile and oral administration of (S)-4f to ...

An ethylene glycol solution was used as the electrophoretic running buffer in unmodified cyclic olefin copolymer (COC) microchips to minimize the interactions between the analytes and the hydrophobic walls of the plastic microchannels, enhance the resolution of the analytes and eliminate the uncontrollable dispersion caused by uneven liquid levels and ...

An ability of donor-acceptor cyclopropanes to (3+3)-cyclodimerization was disclosed. It was found that Lewis acid-induced transformations of 2-(hetero)arylcyclopropane-1,1-dicarboxylates containing electron-abundant aromatic substituents led to the construction of six-membered cyclic systems. Depending on the substrate properties and the Lewis acid applied three types of products can be obtained: 1) 1,4-diarylcyclohexanes, 2) ...

Chromone derivatives were synthesized from 2,3-allenoic acids and benzynes in moderate to excellent yields under mild conditions. Instead of the cyclic conjugate addition of the intermediate A formed by the nucleophilic addition of allenoic acid with benzyne, this intermediate undergoes 1,2-addition with the carbonyl group, which was followed by the ...

The polyetherification of diols with 4-12 methylene units was studied in Brønsted Acid Ionic Liquids (BAILs). High molar mass poly(oxyalkylene)s were obtained at relatively low temperatures (130 °C), except in the cases of 1,4-butanediol and 1,6-hexanediol where cyclic ether formation was observed.

Szentiamide (1) a new cyclic hexadepsipeptide was isolated from the culture broth of the entomopathogenic bacterium Xenorhabdus szentirmaii DSM 16338T. The structure was elucidated by analysis of one- and two-dimensional NMR spectra and high resolution mass spectrometry. The amino acids were determined to be D-leucine, L-threonine, D-phenylalanine, D-valine, L-tyrosine and ...

A series of acidic triazoles with activity as soluble guanylate cyclase stimulators is described. Incorporation of the CF(3) triazole improved the overall physicochemical and drug-like properties of the molecule and is exemplified by compound 25.

The synthesis and catalytic activity of three well-defined monomeric rhodium(i) hydroxide complexes bearing N-heterocyclic carbene (NHC) ligands are reported. [Rh(cod)(ICy)(OH)] promoted the 1,4-addition of arylboronic acids to cyclic enones, with TONs and TOFs of 100,000 and 6,600 h(-1), respectively, at 0.001 mol% catalyst loadings. Mechanistic studies permitted the isolation of ...

In the crystal structure of the title mol-ecular adduct, C(9)H(7)N·C(8)H(12)O(4), the two species are -linked through a carb-oxy-lic acid-isoquinoline O-H⋯N hydrogen bond. These mol-ecular pairs then inter-associate through the second acid group of the cis-cyclo-hexane-1,2-dicarb-oxy-lic acid molecules, forming a classic centrosymmetric cyclic head-to-head carb-oxy-lic acid-carboxyl O-H⋯O hydrogen-bonding association [graph-set R(2) ...

A chiral Brønsted acid has been developed from a cationic gold(I) disphosphine complex in the presence of alcoholic solvent and applied to the enantioselective protonation reaction of silyl enol ethers of ketones. Various optically active cyclic ketones were obtained in excellent yields and high enantioselectivities, including cyclic ketones bearing aliphatic ...

Grassypeptolides F (1) and G (2), bis-thiazoline-containing cyclic depsipeptides with a rare β-amino acid, extensive N-methylation, and a large number of d-amino acids, are reported from an extract of the Palauan cyanobacterium Lyngbya majuscula. Both 1 and 2 were found to have moderate inhibitory activity against the transcription factor AP-1 ...

BACKGROUND: Paeonia lactiflora root (baishao in Chinese) is a commonly used herb in TCM. Research has shown baishao to have positive pharmacological actions, including, particularly, anti-inflammatory properties. In this paper we studied the influence of baishao extract on cAMP-phosphodiesterase (PDE) activity and related anti-inflammatory action to identify new pharmacologic action ...

A Rh-based catalytic system implying electron-poor MeOBIPHEP analogues has been developed for the 1,4-addition of boronic acids to maleimides and enones under mild conditions at room temperature and led to succinimide derivatives and arylated cyclic ketones in good to excellent yields and ee. We uncovered the crucial role of the ...

Four cyclic decapeptides, minutissamides A-D (1-4), were isolated from the cultured cyanobacterium Anabaena minutissima (UTEX 1613). The planar structures were determined using various spectroscopic techniques including HRESIMS and 1D and 2D NMR experiments. The absolute configurations of the α-amino acid residues were assigned using Marfey's method after acid hydrolysis. The ...

NMR-guided fractionation of a non-polar extract of a Florida Keys collection of Lyngbya sp. resulted in the isolation of two novel epimeric cyclic depsipeptides, porpoisamides A (1) and B (2). The planar structures of these compounds were determined using NMR spectroscopic techniques. The absolute configurations of amino and hydroxy acid ...

The naturally occurring cyclic tetrapeptide, chlamydocin, originally isolated from fungus Diheterospora chlamydosphoria, consists of α-aminoisobutyric acid, L: -phenylalanine, D: -proline and an unusual amino acid (S)-2-amino-8-((S)-oxiran-2-yl)-8-oxooctanoic acid (Aoe) and inhibits the histone deacetylases (HDACs), a class of regulatory enzymes. The epoxyketone moiety of Aoe is the key functional group for ...

Carcinomas are considered to be associated with increased cellular proliferation under antigenic stimulation and inflammation. Therefore, the markers of increased cellular turnover such as adenosine deaminase and uric acid were estimated quantitatively along with markers of inflammation such as C-reactive protein in squamous cell carcinoma of head and neck region. ...

The method of Kouklovsky and coworkers for the enantioselective alkylation of cyclic N-naphthoyl derivatives of amino acids was used to introduce a (13)C label into one of the two enantiotopic methyl groups of 2-aminoisobutyric acid (Aib) by retentive alkylation of L-alanine with (13)CH(3)I. Conditions were identified for optimization of yield ...

BACKGROUND: The present study investigated the effect of irradiation, active and modified atmosphere packaging, and storage conditions on quality retention of raw, whole, unpeeled almonds. Almond kernels were packaged in barrier and high-barrier pouches, under N(2) or with an O(2) absorber and stored either under fluorescent lighting or in the ...

The present study investigated the effect of irradiation, active and modified atmosphere packaging, and storage conditions on quality retention of raw, whole, unpeeled almonds. Almond kernels were packaged in barrier and high-barrier pouches, under N(2) or with an O(2) absorber and stored either under fluorescent lighting or in the dark ...

Autophagy is an intracellular catabolic process that responds with great sensitivity to nutrient availability, implying that certain macro- or micro-nutrients are involved. We found that retinoic acid promotes autophagosome maturation through a pathway independent from the classic nuclear retinoid receptors. Retinoic acid redistributes the cation-independent mannose-6-phosphate receptor from the trans-Golgi ...

The fusion oncogene, promyelocytic leukaemia (PML)-retinoic acid receptor-α (RARA), initiates acute promyelocytic leukaemia (APL) through both a block to differentiation and increased self-renewal of leukaemic progenitor cells. The current standard of care is retinoic acid (RA) and chemotherapy, but arsenic trioxide also cures many patients with APL, and an RA ...

Glial fibrillary acidic protein (GFAP) is the main astroglial marker during astrogliogenesis, but it is also expressed in other cell types, including neural stem cells and old neurons. Activation of the JAK/STAT pathway by the IL-6 family of cytokines is the canonical pathway regulating GFAP expression, whereas retinoic acid is ...

Mice deficient in growth differentiation factor 11 (GDF11) signaling display anterior transformation of axial vertebrae and truncation of caudal vertebrae. However, the in vivo molecular mechanisms by which GDF11 signaling regulates the development of the vertebral column have yet to be determined. We found that Gdf11 and Acvr2b mutants are ...

The bisdichloroacetyldiamine WIN 18,446 reversibly inhibits spermatogenesis in many species, including humans; however, the mechanism by which WIN 18,446 functions is unknown. As retinoic acid is essential for spermatogenesis, we hypothesized that WIN 18,446 might inhibit retinoic acid biosynthesis from retinol (vitamin A) within the testes by inhibiting the enzyme ...

A 15-year-old Caucasian boy with a diagnosis of confluent and reticulated papillomatosis who had received numerous treatments with minimal responses cleared with a 20-week course of 13-cis-retinoic acid and has remained in remission. It is important to consider the use of oral retinoids in the treatment of this stubborn, unsightly, ...

To develop a targeted drug delivery system for cancer therapy and anti-angiogenesis, amphiphilic heparin bioconjugates were synthesized by chemical conjugation of hydrophobic retinoic acid and a targeting ligand, folic acid, to the heparin backbone (HFR). The chemical structure of the HFR conjugates was confirmed by proton nuclear magnetic resonance ((1)H ...

The binding of all-trans retinoic acid (ATRA) to retinoid receptor-alpha (RAR-alpha) relieves transcriptional repression induced by the promyelocytic leukemia-retinoic acid receptor (PML-RAR) oncoprotein. The ATRA molecule contains a cyclohexenyl ring, a polyene chain containing conjugated double alkene bonds, and a terminal carboxyl group. To determine the contributions of these structural ...

Inflammatory bowel disease is characterized with uncontrolled immune response in inflamed mucosa, with dominance of Th1 cells. Recently, all-trans retinoic acid has been shown that can lead T-cell response by suppressing Th17 development via retinoic acid receptor (RAR), but it is still unknown whether all-trans retinoic acid can modulate Th1 ...

The retinoids, a group of natural or synthetic derivatives of vitamin A, exert various anti-neoplastic and immunomodulatory actions. Recent studies have demonstrated that retinoic acid protects rats against lipopolysaccharide (LPS)-induced mastitis, but the mechanism of action is unclear. In the present study, an LPS-induced rat mastitis model and primary cultures ...

The human COX-2 promoter contains a direct repeat 1 (DR1) which was shown to confer responsiveness to PPARs. We found that in AN(3)CA and F9 cells, this hCOX-2 DR1 mediates responsiveness to all-trans-retinoic acid (tRA) or 9-cis-retinoic acid (9cRA), but this effect was suppressed by PPARδ. Truncated PPARδ lacking the ...

Retinoic acid and bone morphogenetic protein (BMP4) are endogenous factors indispensable for the physiological development of vertebrates. The proximate aim of the present study was to investigate whether the natural compound citral (a retinoic acid synthesis inhibitor) and a monoclonal, anti-BMP4 antibody, administered to pregnant mice affect in the fetuses ...

One of the most notable features of the vertebrate body plan organization is its bilateral symmetry, evident at the level of vertebrae and skeletal muscles. Here we show that a mutation in Rere (also known as atrophin2) leads to the formation of asymmetrical somites in mouse embryos, similar to embryos ...

The importance of dietary fat components, such as fatty acids, in the expression of multiple genes is clear. In the case of beef cattle, fat in the form of fatty acids (saturated or unsaturated), vitamin A (mainly retinoic acid), or carotenoids (beta-carotene and lutein) is obtained from dietary feed or ...

AIM: Neuroblastoma is an important pediatric tumor in which Myc-N amplification is a well-known poor prognostic indicator. It has a great diversity in clinical behavior. The effect of pharmacologic agents used in neuroblastoma treatment on Myc-N expression is still unclear. METHOD: We analyzed Myc-N expression changes by immunocytochemistry in Myc-N-positive ...

Acute promyelocytic leukemia (ARL) is characterized by the nearly homogeneous expression of the fusion oncogenic protein PML-RARalpha and the testis-specific cyclin A1 protein, which are implicated in its pathogenesis. PML-RARalpha binds all-trans retinoic acid with high affinity inducing granulocytic differentiation and remission. Current approaches with high doses of single or ...

In this review, we focus on processes, organs and systems targeted by the marine toxins yessotoxin (YTX), okadaic acid (OA) and palytoxin (PTX). The effects of YTX and their basis are analyzed from data collected in the mollusc Mytilus galloprovincialis, the annelid Enchytraeus crypticus, Swiss CD1 mice and invertebrate and ...

Alcian blue skeletal preparations of wild-type (front) and retinoic acid-treated (back) embryos of the little skate, Leucoraja erinacea. As in paired fins, the cartilaginous gill rays of L. erinacea are patterned by a retinoic acid-regulated Sonic hedghog (Shh)-Fibroblast growth factor 8 (Fgf8) feedback loop, and exposure to exogenous retinoic acid ...

Retinoic acid, an essential factor derived from vitamin A, has been shown to have a variety of functions including roles as an antioxidant and in cellular differentiation. Since oxidative stress and dedifferentiation of neurons appear to be common pathological elements of a number of neurodegenerative disorders, we speculated that retinoic ...

The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated ...

To identify potential biomarkers of therapy response, we have previously done a large-scale gain-of-function genetic screen to identify genes whose expression confers resistance to histone deacetylase inhibitors (HDACI). This genetic screen identified two genes with a role in retinoic acid signaling, suggesting that HDACIs target retinoic acid signaling as part ...

Ecotropic viral integration site 1 (EVI1) plays important roles in leukaemia and development, and its expression is temporally and spatially highly restricted during the latter process. Nevertheless, the only physiological agent that to date has been shown to regulate transcription of this gene in mammalian cells is all-trans retinoic acid. ...

The physiology of two metabolites of vitamin A is understood in substantial detail: retinaldehyde functions as the universal chromophore in the vertebrate and invertebrate eye; retinoic acid regulates a set of vertebrate transcription factors, the retinoic acid receptor superfamily. The third member of this retinoid triumvirate is retinol. While functioning ...

All-trans retinoic acid (ATRA), an active metabolite of vitamin A, is widely used in the treatment of acute promyelocytic leukaemia and myelodysplastic syndrome. However, its high lipophilicity is thought to be responsible for the slow dissolution and low bioavailability following oral administration. In order to obtain compounds with better solubility ...