ChemInform Abstract: Linear Synthesis of a Protected H-Type II Pentasaccharide Using Glycosyl Phosphate Building Blocks.

Fluorine is a critical element for the design of bioactive compounds, but its incorporation with high regio- and stereoselectivity using environmentally friendly reagents and catalysts remains an area of development. Stereogenic tertiary fluorides pose a particular synthetic challenge and are thus present in only a few approved pharmaceuticals such as fluticasone, solithromycin, and sofosbuvir. The aldol reaction of fluorinated donors provides an atom-economical approach to asymmetric C-F motifs via C-C bond formation. Here we report that the type II pyruvate aldolase HpcH and engineered mutants thereof are biocatalysts for carboligation of ß-fluoro-α-ketoacids (including fluoropyruvate, ß-fluoro-α-ketobutyrate, and ß-fluoro-α-ketovalerate) with many diverse aldehydes. The reaction proceeds with kinetic resolution in the case of racemic donors. The reactivity of HpcH towards these new donors, which are non-native in both steric and electronic properties, grants access to enantiopure fragments with secondary or tertiary fluoride stereocenters. In addition to representing the first asymmetric synthesis of tertiary fluorides via biocatalytic carboligation, the afforded products could improve the diversity of fluorinated building blocks and enable the synthesis of fluorinated drug analogs.

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Structural characterization of hexameric shell proteins from two types of choline-utilization bacterial microcompartments

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x21007470 ◽

2021 ◽

Vol 77 (9) ◽

Author(s):

Jessica M. Ochoa ◽

Oscar Mijares ◽

Andrea A. Acosta ◽

Xavier Escoto ◽

Nancy Leon-Rivera ◽

...

Keyword(s):

Structural Characterization ◽

Building Blocks ◽

Type I ◽

Type Ii ◽

Protein Subunits ◽

Bacterial Microcompartments ◽

Bacterial Microcompartment ◽

Glycyl Radical ◽

Shell Proteins

Bacterial microcompartments are large supramolecular structures comprising an outer proteinaceous shell that encapsulates various enzymes in order to optimize metabolic processes. The outer shells of bacterial microcompartments are made of several thousand protein subunits, generally forming hexameric building blocks based on the canonical bacterial microcompartment (BMC) domain. Among the diverse metabolic types of bacterial microcompartments, the structures of those that use glycyl radical enzymes to metabolize choline have not been adequately characterized. Here, six structures of hexameric shell proteins from type I and type II choline-utilization microcompartments are reported. Sequence and structure analysis reveals electrostatic surface properties that are shared between the four types of shell proteins described here.

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Identification of an Archaeal Type II Isopentenyl Diphosphate Isomerase in Methanothermobacter thermautotrophicus

Journal of Bacteriology ◽

10.1128/jb.186.6.1811-1817.2004 ◽

2004 ◽

Vol 186 (6) ◽

pp. 1811-1817 ◽

Cited By ~ 30

Author(s):

Sam J. Barkley ◽

Rita M. Cornish ◽

C. Dale Poulter

Keyword(s):

Mevalonate Pathway ◽

Specific Activity ◽

Building Blocks ◽

Flavin Mononucleotide ◽

Ionization Mass ◽

Type I ◽

Isopentenyl Diphosphate ◽

Type Ii ◽

Methanothermobacter Thermautotrophicus

ABSTRACT Isopentenyl diphosphate (IPP):dimethylallyl diphosphate isomerase catalyzes the interconversion of the fundamental five-carbon homoallylic and allylic diphosphate building blocks required for biosynthesis of isoprenoid compounds. Two different isomerases have been reported. The type I enzyme, first characterized in the late 1950s, is widely distributed in eukaryota and eubacteria. The type II enzyme was recently discovered in Streptomyces sp. strain CL190. Open reading frame 48 (ORF48) in the archaeon Methanothermobacter thermautotrophicus encodes a putative type II IPP isomerase. A plasmid-encoded copy of the ORF complemented IPP isomerase activity in vivo in Salmonella enterica serovar Typhimurium strain RMC29, which contains chromosomal knockouts in the genes for type I IPP isomerase (idi) and 1-deoxy-d-xylulose 5-phosphate (dxs). The dxs gene was interrupted with a synthetic operon containing the Saccharomyces cerevisiae genes erg8, erg12, and erg19 allowing for the conversion of mevalonic acid to IPP by the mevalonate pathway. His6-tagged M. thermautotrophicus type II IPP isomerase was produced in Escherichia coli and purified by Ni2+ chromatography. The purified protein was characterized by matrix-assisted laser desorption ionization mass spectrometry. The enzyme has optimal activity at 70°C and pH 6.5. NADPH, flavin mononucleotide, and Mg2+ are required cofactors. The steady-state kinetic constants for the archaeal type II IPP isomerase from M. thermautotrophicus are as follows: Km , 64 μM; specific activity, 0.476 μmol mg−1 min−1; and k cat, 1.6 s−1.

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A theoretical study on the electronic properties of in-plane CdS/ZnSe heterostructures: type-II band alignment for water splitting

Journal of Materials Chemistry A ◽

10.1039/c7ta10624f ◽

2018 ◽

Vol 6 (9) ◽

pp. 4161-4166 ◽

Cited By ~ 50

Author(s):

Hongchao Yang ◽

Jinjin Li ◽

Lin Yu ◽

Baibiao Huang ◽

Yandong Ma ◽

...

Keyword(s):

Electronic Properties ◽

Water Splitting ◽

Materials Science ◽

Theoretical Study ◽

Building Blocks ◽

Band Alignment ◽

Device Physics ◽

Type Ii ◽

Two Dimensional

Lateral heterostructures fabricated by using two-dimensional (2D) building blocks have attracted a great deal of attention in materials science and device physics.

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Regiocontrolled [3 + 2] Quinone-Nitrile Oxide Entry to Type II Polyketide Building Blocks.

ChemInform ◽

10.1002/chin.200410126 ◽

2004 ◽

Vol 35 (10) ◽

Author(s):

Joel L. Stevens ◽

Thomas D. Welton ◽

Jay P. Deville ◽

Victor Behar

Keyword(s):

Building Blocks ◽

Nitrile Oxide ◽

Type Ii

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Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology?

Biochemical Society Transactions ◽

10.1042/bst0331041 ◽

2005 ◽

Vol 33 (5) ◽

pp. 1041-1044 ◽

Cited By ~ 103

Author(s):

G.J. Biessels ◽

L.J. Kappelle

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Type Ii Diabetes ◽

Brain Aging ◽

Building Blocks ◽

Type Ii ◽

The Metabolic Syndrome ◽

Increased Risk ◽

The Brain

Type II diabetes mellitus (DM2) is associated with an increased risk of cognitive dysfunction and dementia. The increased risk of dementia concerns both Alzheimer's disease and vascular dementia. Although some uncertainty remains into the exact pathogenesis, several mechanisms through which DM2 may affect the brain have now been identified. First, factors related to the ‘metabolic syndrome’, a cluster of metabolic and vascular risk factors (e.g. dyslipidaemia and hypertension) that is closely linked to DM2, may be involved. A number of these risk factors are predictors of cerebrovascular disease, accelerated cognitive decline and dementia. Secondly, hyperglycaemia may be involved, through adverse effects of potentially ‘toxic’ glucose metabolites on the brain and its vasculature. Thirdly, insulin itself may be involved. Insulin can directly modulate synaptic plasticity and learning and memory, and disturbances in insulin signalling pathways in the periphery and in the brain have recently been implicated in Alzheimer's disease and brain aging. Insulin also regulates the metabolism of β-amyloid and tau, the building blocks of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease. In this paper, the evidence for the association between DM2 and dementia and for each of these underlying mechanisms will be reviewed, with emphasis on the role of insulin itself.

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Autophagy: A Potential Therapeutic Target of Polyphenols in Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers12030562 ◽

2020 ◽

Vol 12 (3) ◽

pp. 562 ◽

Cited By ~ 7

Author(s):

Chandramohan Kiruthiga ◽

Kasi Pandima Devi ◽

Seyed M. Nabavi ◽

Anupam Bishayee

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Death ◽

Liver Cancer ◽

Cancer Cells ◽

Building Blocks ◽

Polyphenolic Compounds ◽

Beclin 1 ◽

Type Ii ◽

Hepatic Diseases ◽

Topographical Distribution

Autophagy is a conserved biological phenomenon that maintains cellular homeostasis through the clearing of damaged cellular components under cellular stress and offers the cell building blocks for cellular survival. Aberrations in autophagy subsidize to various human pathologies, such as dementia, cardiovascular diseases, leishmaniosis, influenza, hepatic diseases, and cancer, including hepatocellular carcinoma (HCC). HCC is the fifth common mortal type of liver cancer globally, with an inhomogeneous topographical distribution and highest incidence tripled in men than women. Existing treatment procedures with liver cancer patients result in variable success rates and poor prognosis due to their drug resistance and toxicity. One of the pathophysiological mechanisms that are targeted during the development of anti-liver cancer drugs is autophagy. Generally, overactivated autophagy may lead to a non-apoptotic form of programmed cell death (PCD) or autophagic cell death or type II PCD. Emerging evidence suggests that manipulation of autophagy could induce type II PCD in cancer cells, acting as a potential tumor suppressor. Hence, altering autophagic signaling offers new hope for the development of novel drugs for the therapy of resistant cancer cells. Natural polyphenolic compounds, including flavonoids and non-flavonoids, execute their anticarcinogenic mechanism through upregulating tumor suppressors and autophagy by modulating canonical (Beclin-1-dependent) and non-canonical (Beclin-1-independent) signaling pathways. Additionally, there is evidence signifying that plant polyphenols target angiogenesis and metastasis in HCC via interference with multiple intracellular signals and decrease the risk against HCC. The current review offers a comprehensive understanding of how natural polyphenolic compounds exhibit their anti-HCC effects through regulation of autophagy, the non-apoptotic mode of cell death.

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