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Cell Chemical Biology Nov 2023Stimulator of interferon genes (STING) agonists are promising candidates for vaccine adjuvants and antitumor immune stimulants. The most potent natural agonist of STING,...
Stimulator of interferon genes (STING) agonists are promising candidates for vaccine adjuvants and antitumor immune stimulants. The most potent natural agonist of STING, 2',3'-cyclic GMP-AMP (2',3'-cGAMP), is subject to nuclease-mediated inherent metabolic instability, thereby placing limits on its clinical efficacy. Here, we report on a new class of chemically synthesized sugar-modified analogs of 2',3'-cGAMP containing arabinose and xylose sugar derivatives that bind mouse and human STING alleles with high affinity. The co-crystal structures demonstrate that such analogs act as 2',3'-cGAMP mimetics that induce the "closed" conformation of human STING. These analogs show significant resistance to hydrolysis mediated by ENPP1 and increased stability in human serum, while retaining similar potency as 2',3'-cGAMP at inducing IFN-β secretion from human THP1 cells. The arabinose- and xylose-modified 2',3'-cGAMP analogs open a new strategy for overcoming the inherent nuclease-mediated vulnerability of natural ribose cyclic nucleotides, with the additional benefit of high translational potential as cancer therapeutics and vaccine adjuvants.
Topics: Humans; Animals; Mice; Arabinose; Xylose; Adjuvants, Vaccine; Nucleotides, Cyclic
PubMed: 37536341
DOI: 10.1016/j.chembiol.2023.07.002 -
Journal of Plant Research Sep 2016L-Arabinose (L-Ara) is a plant-specific sugar accounting for 5-10 % of cell wall saccharides in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). L-Ara occurs... (Review)
Review
L-Arabinose (L-Ara) is a plant-specific sugar accounting for 5-10 % of cell wall saccharides in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). L-Ara occurs in pectic arabinan, rhamnogalacturonan II, arabinoxylan, arabinogalactan-protein (AGP), and extensin in the cell walls, as well as in glycosylated signaling peptides like CLAVATA3 and small glycoconjugates such as quercetin 3-O-arabinoside. This review focuses on recent advances towards understanding the generation of L-Ara and the metabolism of L-Ara-containing molecules in plants.
Topics: Arabinose; Models, Biological; Phylogeny; Plants; Pollen; Uridine Diphosphate
PubMed: 27220955
DOI: 10.1007/s10265-016-0834-z -
Plant & Cell Physiology Dec 2021Growth, development, structure as well as dynamic adaptations and remodeling processes in plants are largely controlled by properties of their cell walls. These... (Review)
Review
Growth, development, structure as well as dynamic adaptations and remodeling processes in plants are largely controlled by properties of their cell walls. These intricate wall structures are mostly made up of different sugars connected through specific glycosidic linkages but also contain many glycosylated proteins. A key plant sugar that is present throughout the plantae, even before the divergence of the land plant lineage, but is not found in animals, is l-arabinose (l-Ara). Here, we summarize and discuss the processes and proteins involved in l-Ara de novo synthesis, l-Ara interconversion, and the assembly and recycling of l-Ara-containing cell wall polymers and proteins. We also discuss the biological function of l-Ara in a context-focused manner, mainly addressing cell wall-related functions that are conferred by the basic physical properties of arabinose-containing polymers/compounds. In this article we explore these processes with the goal of directing future research efforts to the many exciting yet unanswered questions in this research area.
Topics: Arabinose; Cell Wall; Plants
PubMed: 34129041
DOI: 10.1093/pcp/pcab087 -
Applied Microbiology and Biotechnology Mar 2011L-Arabinose is the second most abundant pentose beside D-xylose and is found in the plant polysaccharides, hemicellulose and pectin. The need to find renewable carbon... (Review)
Review
L-Arabinose is the second most abundant pentose beside D-xylose and is found in the plant polysaccharides, hemicellulose and pectin. The need to find renewable carbon and energy sources has accelerated research to investigate the potential of L-arabinose for the development and production of biofuels and other bioproducts. Fungi produce a number of extracellular arabinanases, including α-L-arabinofuranosidases and endo-arabinanases, to specifically release L-arabinose from the plant polymers. Following uptake of L-arabinose, its intracellular catabolism follows a four-step alternating reduction and oxidation path, which is concluded by a phosphorylation, resulting in D-xylulose 5-phosphate, an intermediate of the pentose phosphate pathway. The genes and encoding enzymes L-arabinose reductase, L-arabinitol dehydrogenase, L-xylulose reductase, xylitol dehydrogenase, and xylulokinase of this pathway were mainly characterized in the two biotechnological important fungi Aspergillus niger and Trichoderma reesei. Analysis of the components of the L-arabinose pathway revealed a number of specific adaptations in the enzymatic and regulatory machinery towards the utilization of L-arabinose. Further genetic and biochemical analysis provided evidence that L-arabinose and the interconnected D-xylose pathway are also involved in the oxidoreductive degradation of the hexose D-galactose.
Topics: Arabinose; Aspergillus niger; Metabolic Networks and Pathways; Polysaccharides; Trichoderma
PubMed: 21212945
DOI: 10.1007/s00253-010-3071-8 -
Carbohydrate Research Apr 2023A new synthesis of rare d-lyxose from easily available d-arabinose is disclosed. The route includes 7 steps with a total 40% yield. Inversion of configuration at C3...
A new synthesis of rare d-lyxose from easily available d-arabinose is disclosed. The route includes 7 steps with a total 40% yield. Inversion of configuration at C3 promoted by DAST reagent is utilized on trans-2,3-di-hydroxy pentofuranose to provide cis-2,3-di-hydroxy pentofuranose, which is hardly synthesized using normal method.
Topics: Arabinose; Pentoses
PubMed: 37001234
DOI: 10.1016/j.carres.2023.108782 -
Bioprocess and Biosystems Engineering Jun 2021L-Ribose, a starting material for the synthesis of L-nucleoside, has attracted lots of attention since L-nucleoside is responsible for the antiviral activities of the...
L-Ribose, a starting material for the synthesis of L-nucleoside, has attracted lots of attention since L-nucleoside is responsible for the antiviral activities of the racemic mixtures of nucleoside enantiomers. In this study, the L-ribulose-producing Candida tropicalis strain was engineered for the conversion of L-arabinose to L-ribose. For the construction of a uracil auxotroph, the URA3 gene was excised by homologous recombination. The expression cassette of codon-optimized L-ribose isomerase gene from Acinetobacter calcoaceticus DL-28 under the control of the GAPDH promoter was integrated to the uracil auxotroph. The resulting strain, K1 CoSTP2 LsaAraA AcLRI, was cultivated with the glucose/L-arabinose mixture. At 45.5 h of fermentation, 6.0 g/L of L-ribose and 3.2 g/L of L-ribulose were produced from 30 g/L of L-arabinose. The proportion between L-ribose and L-ribulose was approximately 2:1 and the conversion yield of L-arabinose to L-ribose was about 20% (w/w). The L-ribose-producing yeast strain was successfully constructed for the first time and could convert L-arabinose to L-ribose in one-pot fermentation using the mixture of glucose and L-arabinose.
Topics: Arabinose; Candida tropicalis; Microorganisms, Genetically-Modified; Ribose
PubMed: 33559750
DOI: 10.1007/s00449-020-02506-2 -
Biochemical and Biophysical Research... May 2022l-Arabinose 1-dehydrogenase (AraDH) catalyzes the NAD(P)-dependent oxidation of l-arabinose to L-arabinono-1,4-lactone in the non-phosphorylative l-arabinose pathway,...
l-Arabinose 1-dehydrogenase (AraDH) catalyzes the NAD(P)-dependent oxidation of l-arabinose to L-arabinono-1,4-lactone in the non-phosphorylative l-arabinose pathway, and is classified into glucose-fructose oxidoreductase and short-chain dehydrogenase/reductase (SDR). We herein report the crystal structure of a SDR-type AraDH (from Herbaspirillum huttiense) for the first time. The interactions between Asp49 and the 2'- and 3'-hydroxyl groups of NAD were consistent with strict specificity for NAD. In a binding model for the substrate, Ser155 and Tyr168, highly conserved in the SDR superfamily, interacted with the C1 and/or C2 hydroxyl(s) of l-arabinose, whereas interactions between Asp107, Arg109, and Gln206 and the C2 and/or C3 hydroxyl(s) were unique to AraDH. Trp200 significantly contributed to the selectivities of the C4 hydroxyl and C6 methyl of substrates.
Topics: Arabinose; NAD; Oxidoreductases; Short Chain Dehydrogenase-Reductases; Substrate Specificity
PubMed: 35279441
DOI: 10.1016/j.bbrc.2022.03.028 -
Pharmacological Research Apr 2024CREB-regulated transcription coactivator 1 (CRTC1), a pivotal synaptonuclear messenger, regulates synaptic plasticity and transmission to prevent depression. Despite...
CREB-regulated transcription coactivator 1 (CRTC1), a pivotal synaptonuclear messenger, regulates synaptic plasticity and transmission to prevent depression. Despite exhaustive investigations into CRTC1 mRNA reductions in the depressed mice, the regulatory mechanisms governing its transcription remain elusive. Consequently, exploring rapid but non-toxic CRTC1 inducers at the transcriptional level is important for resisting depression. Here, we demonstrate the potential of D-arabinose, a unique monosaccharide prevalent in edible-medicinal plants, to rapidly enter the brain and induce CRTC1 expression, thereby eliciting rapid-acting and persistent antidepressant responses in chronic restrain stress (CRS)-induced depressed mice. Mechanistically, D-arabinose induces the expressions of peroxisome proliferator-activated receptor gamma (PPARγ) and transcription factor EB (TFEB), thereby activating CRTC1 transcription. Notably, we elucidate the pivotal role of the acetyl-CoA synthetase short-chain family member 2 (ACSS2) as an obligatory mediator for PPARγ and TFEB to potentiate CRTC1 transcription. Furthermore, D-arabinose augments ACSS2-dependent CRTC1 transcription by activating AMPK through lysosomal AXIN-LKB1 pathway. Correspondingly, the hippocampal down-regulations of ACSS2, PPARγ or TFEB alone failed to reverse CRTC1 reductions in CRS-exposure mice, ultimately abolishing the anti-depressant efficacy of D-arabinose. In summary, our study unveils a previously unexplored role of D-arabinose in activating the ACSS2-PPARγ/TFEB-CRTC1 axis, presenting it as a promising avenue for the prevention and treatment of depression.
Topics: Mice; Animals; PPAR gamma; Arabinose; Transcription Factors; Antidepressive Agents; Brain
PubMed: 38460778
DOI: 10.1016/j.phrs.2024.107136 -
Trends in Genetics : TIG Dec 2000Over forty years of research on the L-arabinose operon of Escherichia coli have provided insights into the mechanism of positive regulation of gene activity. This... (Review)
Review
Over forty years of research on the L-arabinose operon of Escherichia coli have provided insights into the mechanism of positive regulation of gene activity. This research also discovered DNA looping and the mechanism by which the regulatory protein changes its DNA-binding properties in response to the presence of arabinose. As is frequently seen in focused research on biological subjects, the initial studies were primarily genetic. Subsequently, the genetic approaches were augmented by physiological and then biochemical studies. Now biophysical studies are being conducted at the atomic level, but genetics still has a crucial role in the study of this system.
Topics: Arabinose; Escherichia coli; Operon
PubMed: 11102706
DOI: 10.1016/s0168-9525(00)02153-3 -
Anaerobe Jun 2022Biofilm formation on dental implant surfaces can cause peri-implant mucositis and peri-implantitis. Lectins are involved in interactions between bacteria or between...
OBJECTIVES
Biofilm formation on dental implant surfaces can cause peri-implant mucositis and peri-implantitis. Lectins are involved in interactions between bacteria or between bacteria and their hosts. Disrupting these interactions via specific sugars can result in reduced adhesion and biofilm formation. The purpose of this study was to identify sugars that function as antiadhesion or antibiofilm agents on titanium discs.
METHODS
Of the sugars tested, the sugars that did not affect the planktonic growth of Streptococcus oralis, Fusobacterium nucleatum, and Porphyromonas gingivalis were selected. The selected sugars were assessed for their ability to inhibit biofilm formation of bacteria in single and consortium species by crystal violet staining, confocal laser scanning microscopy after live/dead staining, and scanning electron microscopy. The sugars were evaluated for their ability to inhibit activity of the quorum sensing molecule autoinducer 2 (AI-2) by bioluminescence assay.
RESULTS
Biofilm formation of single bacteria or consortia of S. oralis, F. nucleatum, and P. gingivalis on titanium discs was significantly inhibited in the presence of d-arabinose. Pretreating titanium discs with d-arabinose for 3 min inhibited biofilm formation at a level comparable to that observed when d-arabinose was present over the entire period, suggesting that d-arabinose had initial anti-adhesive activity. In addition, d-arabinose inhibited the activity of AI-2.
CONCLUSIONS
d-Arabinose may be a good candidate for application as an antibiofilm agent and AI-2 inhibitor.
Topics: Arabinose; Biofilms; Fusobacterium nucleatum; Humans; Peri-Implantitis; Porphyromonas gingivalis; Titanium
PubMed: 35143955
DOI: 10.1016/j.anaerobe.2022.102533