Design and synthesis of novel tweezer anion receptors based on deoxycholic acid

A novel type of molecular tweezer receptors based on deoxycholic acid has been designed and synthesized and their binding properties were examined by UV-vis spectral titration. These molecular tweezers showed a high selectivity toward F^- over Cl^-, Br^-, I^-, AcO^-, H2PO4^-.

Design and Synthesis of Chiral Molecular Tweezers Based on Deoxycholic Acid

A series of new chiral molecular tweezers have been designed and synthesized by using deoxycholic acid as spacer and aromatic amines as arms. Instead of using toxic phosgene, the triphosgene was employed in synthesis of the molecular tweezers receptors. These chiral molecular tweezers showed good enantioselectivity for D-amino acid methyl esters.

Efficient stereoselective hydroxylation of deoxycholic acid by the robust whole-cell cytochrome P450 CYP107D1 biocatalyst

Deoxycholic acid(DCA)has been authorized by the Federal Drug Agency for cosmetic reduction of redundant submental fat.The hydroxylated product(6β-OH DCA)was developed to improve the solubility and pharmaceutic properties of DCA for further applications.Herein,a combinatorial catalytic strategy was applied to construct a powerful Cytochrome P450 biocatalyst(CYP107D1,OleP)to convert DCA to 6β-OH DCA.Firstly,the weak expression of OleP was significantly improved using pRSFDuet-1 plasmid in the E.coli C41(DE3)strain.Next,the supply of heme was enhanced by the moderate overexpression of crucial genes in the heme biosynthetic pathway.In addition,a new biosensor was developed to select the appropriate redox partner.Furthermore,a cost-effective whole-cell catalytic system was constructed,resulting in the highest reported conversion rate of 6β-OH DCA(from 4.8%to 99.1%).The combinatorial catalytic strategies applied in this study provide an efficient method to synthesize high-value-added hydroxylated compounds by P450s.

Bile acids in serum and bile of patients with cholesterol gallstone

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Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis

BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.METHODS According to the inclusion and exclusion criteria,27 patients with ALC and 24 healthy controls(HCs)were selected,and plasma and feces samples were collected.Liver function,blood routine,and other indicators were detected with automatic biochemical and blood routine analyzers.Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces.Also,the correlation between metabolites and clinical features was analyzed.RESULTS More than 300 common metabolites were identified in the plasma and feces of patients with ALC.Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways.Compared to HCs,patients with ALC had a higher level of glycocholic acid(GCA)and taurocholic acid(TCA)in plasma and a lower level of deoxycholic acid(DCA)in the feces,while L-threonine,L-phenylalanine,and L-tyrosine increased simultaneously in plasma and feces.GCA,TCA,L-methionine,L-phenylalanine,and L-tyrosine in plasma were positively correlated with total bilirubin(TBil),prothrombin time(PT),and maddrey discriminant function score(MDF)and negatively correlated with cholinesterase(CHE)and albumin(ALB).The DCA in feces was negatively correlated with TBil,MDF,and PT and positively correlated with CHE and ALB.Moreover,we established a P/S BA ratio of plasma primary bile acid(GCA and TCA)to fecal secondary bile acid(DCA),which was relevant to TBil,PT,and MDF score.CONCLUSION The enrichment of GCA,TCA,L-phenylalanine,L-tyrosine,and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC.These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.

Synthesis and Characterization of Chitosan-based Biomateriais Modified with Different Active Groups and Their Relationship with Cytotoxicity

The cytotoxicity profile of three chitosan derivatives with different affinity to water was evaluated in vitro. The derivatives selected were carboxymethylated-chitosan （CMCH）, linoleic acid modifiedchitosan （LACH） and deoxycholic acid modified-chitosan （DACH）, respectively, and the results of FTIR and NMR confirmed the successful modification. Cytotoxicity of these polymers was investigated via the red blood cell lysis assay and the MTT assay. The red blood cell lysis test showed that CH elicited a certain level of red blood cell toxicity, while CMCH, LACH and DACH all displayed low membrane damaging effects, with the hemolysis rates of 2.385%, 1.560% and 4.404%, respectively, which comes well within permissible limit （5%）. The MTT assay revealed that CH exhibited significant inhibitory effect on fibroblast proliferation at higher concentration, while its three derivatives showed no cytotoxicity. CMCH had stimulatory effects on fetal mouse fibroblast proliferation. Differences in cytotoxicity of CH and its derivatives may result from the specific chemical modifications leading to the alteration of molecular charge density and type of the cationic functionalities, structure and sequence, and conformational flexibility.