De Novo Synthesis of the Bacterial 2-Amino-2,6-Dideoxy Sugar Building Blocks d-Fucosamine, d-Bacillosamine, and d-Xylo-6-deoxy-4-ketohexosamine

2012 ◽  
Vol 14 (18) ◽  
pp. 4954-4957 ◽  
Author(s):  
Daniele Leonori ◽  
Peter H. Seeberger
2011 ◽  
Vol 77 (2) ◽  
pp. 870-877 ◽  
Author(s):  
Oliviana Calin ◽  
Rajan Pragani ◽  
Peter H. Seeberger

Synthesis ◽  
2021 ◽  
Author(s):  
Henry P. Caldora ◽  
Sebastian Govaerts ◽  
Shashikant U. Dighe ◽  
Oliver J. Turner ◽  
Daniele Leonori

Here we report a desaturative approach for oxindole synthesis. This method uses simple γ-ester-containing cyclohexanones and primary amine building blocks as coupling partners. A dual photoredox–cobalt manifold is used to generate a secondary aniline that, upon heating, cyclizes with the pendent ester functionality. The process operates under mild conditions and was applied to the modification of several amino acids, the blockbuster drug mexiletine, as well as the formation of dihydroquinolinones.


Author(s):  
Ernests Tomass Auziņš ◽  

The study explored changes in carbon fluxes in the central metabolism of brewer’s yeast in the absence of building blocks such as adenine or nitrogen. These flows provide insight into changes in the central metabolism of brewer’s yeast. It was found that in the absence of a building block, the yeast mainly uses fermentation for growth, producing ethanol. Deletion of Δade1 in purine de novo synthesis reduces ethanol production, and decreased glycerol production in adenine starvation indicates a slowing of central metabolism.


2007 ◽  
Vol 13 (16) ◽  
pp. 4510-4522 ◽  
Author(s):  
Alexander Adibekian ◽  
Pascal Bindschädler ◽  
Mattie S. M. Timmer ◽  
Christian Noti ◽  
Nina Schützenmeister ◽  
...  

2009 ◽  
Vol 422 (3) ◽  
pp. e3-e6 ◽  
Author(s):  
Ann Saada

Deoxyribonucleoside triphosphates (dNTPs) are the building blocks of DNA, and a constant supply is essential for the synthesis and maintenance of both the nuclear and mitochondrial genomes. Antiviral nucleoside analogues and inborn errors of nucleotide metabolism frequently cause dNTP pool imbalances, leading to depletion of mtDNA (mitochondrial DNA) in non-replicating tissues. mtDNA depletion, in turn, causes failure of the mitochondrial respiratory chain, resulting in cellular energy depletion and cell death. Accordingly, it is important to understand the origin and regulation of dNTPs in order to develop safe and effective treatments. In this issue of the Biochemical Journal, Morris et al. have pursued the origin of pyrimidines in perfused adult rat heart. They found no evident role for the nucleotide de novo synthesis pathway and also demonstrated that AZT (3′-azido-3′-deoxythymidine; also known as zidovudine) substantially decreased the TTP pool. Their results underscore the general importance of the mitochondrial deoxyribonucleoside salvage pathway in adult tissues, and particularly in AZT-mediated toxicity. Although the role of nucleoside salvaging versus de novo synthesis in humans remains unclear, the study of tissue cultures and animal models contribute to the understanding of the intricate network of biochemical pathways, maintaining the cellular dNTP supply.


2020 ◽  
Vol 16 ◽  
Author(s):  
Yapeng Lu ◽  
Li Zhu ◽  
Rui Cai ◽  
Yu Li ◽  
Yu Zhao

Background: Podophyllotoxin is a natural lignan which possesses anticancer and antiviral activities. Etoposide and teniposide are semisynthetic glycoside derivatives of podophyllotoxin and are increasingly used in cancer medicine. Objective: The present work was aimed to design and synthesize a series of 2, 4, 5-trideoxyhexopyranosides derivatives of 4’-demethylepipodophyllotoxin as novel anticancer agents. Methods: A divergent de novo synthesis of 2, 4, 5-trideoxyhexopyranosides derivatives of 4’-demethylepipodophyllotoxin has been established via palladium-catalyzed glycosylation. The abilities of synthesized glycosides to inhibit the growth of A549, HepG2, SH-SY5Y, KB/VCR and HeLa cancer cells were investigated by MTT assay. Flow cytometric analysis of cell cycle with propidium iodide DNA staining was employed to observe the effect of compound 5b on cancer cell cycle. Results: Twelve D and L monosaccharides derivatives 5a-5l have been efficiently synthesized in three steps from various pyranone building blocks employing de novo glycosylation strategy. D-monosaccharide 5b showed highest cytotoxicity on five cancer cell lines with the IC50 values from 0.9 to 6.7 mM. It caused HepG2 cycle arrest at G2/M phase in a concentration-dependent manner. Conclusion: The present work leads to the development of novel 2, 4, 5-trideoxyhexopyranosides derivatives of 4’- demethylepipodophyllotoxin. The biological results suggested that the replacement of the glucosyl moiety of etoposide with 2, 4, 5-trideoxyhexopyranosyl is favorable to their cytotoxicity. D-monosaccharide 5b caused HepG2 cycle arrest at G2/M phase in a concentration-dependent manner.


2013 ◽  
Vol 9 ◽  
pp. 332-341 ◽  
Author(s):  
Daniele Leonori ◽  
Peter H Seeberger

The availability of rare monosaccharides that cannot be isolated from natural sources is currently limiting the access to the synthesis and the biological evaluation of complex bacterial cell-surface glycans. Here, we report the synthesis of D- and L-fucosamine building blocks by a de novo approach from L- and D-Garner aldehydes. These differentially protected monosaccharide building blocks were utilized to prepare disaccharides present on the surface of Pseudomonas aeruginosa bacteria.


1993 ◽  
Vol 70 (02) ◽  
pp. 273-280 ◽  
Author(s):  
Janos Kappelmayer ◽  
Satya P Kunapuli ◽  
Edward G Wyshock ◽  
Robert W Colman

SummaryWe demonstrate that in addition to possessing binding sites for intact factor V (FV), unstimulated peripheral blood monocytes also express activated factor V (FVa) on their surfaces. FVa was identified on the monocyte surface by monoclonal antibody B38 recognizing FVa light chain and by human oligoclonal antibodies H1 (to FVa light chain) and H2 (to FVa heavy chain) using immunofluorescence microscopy and flow cytometry. On Western blots, partially cleaved FV could be identified as a 220 kDa band in lysates of monocytes. In addition to surface expression of FVa, monocytes also contain intracellular FV as detected only after permeabilization by Triton X-100 by monoclonal antibody B10 directed specifically to the Cl domain not present in FVa. We sought to determine whether the presence of FV in peripheral blood monocytes is a result of de novo synthesis.Using in situ hybridization, no FV mRNA could be detected in monocytes, while in parallel control studies, factor V mRNA was detectable in Hep G2 cells and CD18 mRNA in monocytes. In addition, using reverse transcriptase and the polymerase chain reaction, no FV mRNA was detected in mononuclear cells or in U937 cells, but mRNA for factor V was present in Hep G2 cells using the same techniques. These data suggest that FV is present in human monocytes, presumably acquired by binding of plasma FV, and that the presence of this critical coagulation factor is not due to de novo synthesis.


1983 ◽  
Vol 49 (02) ◽  
pp. 069-072 ◽  
Author(s):  
U L H Johnsen ◽  
T Lyberg ◽  
K S Galdal ◽  
H Prydz

SummaryHuman umbilical vein endothelial cells in culture synthesize thromboplastin upon stimulation with phytohaemagglutinin (PHA) or the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The thromboplastin activity is further strongly enhanced in a time dependent reaction by the presence of gel-filtered platelets or platelet aggregates. This effect was demonstrable at platelet concentrations lower than those normally found in plasma, it may thus be of pathophysiological relevance. The thromboplastin activity increased with increasing number of platelets added. Cycloheximide inhibited the increase, suggesting that de novo synthesis of the protein component of thromboplastin, apoprotein III, is necessary.When care was taken to remove monocytes no thromboplastin activity and no apoprotein HI antigen could be demonstrated in suspensions of gel-filtered platelets, platelets aggregated with thrombin or homogenized platelets when studied with a coagulation assay and an antibody neutralization technique.


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