Concise and Efficient Synthesis of 2-Acetamido-2-deoxy-β-d-hexopyranosides of Diverse Aminosugars from 2-Acetamido-2-deoxy-β-d-glucose

The furanose acetonide derivative 1 is readily prepared from 2-acetamido-2-deoxy-d-glucose on a large scale without the need for chromatography. Mesylation of 1 provides an efficient, concise, synthetic route to rare 2-acetamido-2-deoxy-β-d-hexopyranosides (2 and 3) via the corresponding methyl 2-acetamido-2-deoxy-3-O-methanesulfonyl-β-d-glucopyranoside and subsequent inversion of configuration by direct displacement or formation of a 3,4-epoxide. Opening of this epoxide by azide provided a direct route to methyl 2-acetamido-4-amino-2,4,6-trideoxy-β-d-gulopyranoside 4. Benzylation of 1 followed by ring expansion to the glucopyranoside, deoxygenation at C-6, and subsequent displacement of a C-4 triflate permitted the synthesis of methyl 2-acetamido-4-amino-2,4,6-trideoxy-β-d-galactopyranoside 5. Methyl 2-acetamido-2-deoxy-β-d-glucopyranoside available from 1 in quantitative yield was readily converted to methyl 2-acetamido-2-deoxy-β-d-galactopyranoside 6 (>60%) by inversion of configuration at C-4. Introduction of a lactyl substituent at C-3 of oxazoline 1 also provides a facile synthesis of the biologically important muramic acid β-glycoside 7. An interesting reaction to convert 2-acetamido-2-deoxyhexopyranosides to the corresponding 2-deoxy-2-tetrazole is also reported

Facile Approach to 2-Acetamido-2-deoxy-β-d-Glucopyranosides via a Furanosyl Oxazoline

A concise and convenient route that may be easily scaled is reported for the preparation of unprotected β-glucopyranosides of N-acetyl-d-glucosamine. Reaction of a wide variety of alcohols with a reactive, readily prepared furanosyl oxazoline under acidic conditions affords the corresponding β-d-glucopyranosides in good to high yields. Primary alcohols gave only β-d-glucopyranosides. A mechanism is proposed for this transformation

Additional file 1 of Reverse-genetics studies of lncRNAs—what we have learnt and paths forward

Additional file 1. Review history

Additional file 1 of Common occurrence of hotspots of single strand DNA breaks at transcriptional start sites

Supplementary Material

Identification and Design of Peptides for the Rapid, High-Yield Formation of Nanoparticulate TiO₂ from Aqueous Solutions at Room Temperature

Titania (TiO2) nanoparticles are widely used, or are under active development, for a range of applications in (photo)catalysis, photovoltaics, enzyme support, energy storage, and photonics. The peptide-directed room-temperature formation of titania nanoparticles can be an attractive alternative to higher-temperature synthetic methods. However, the influence of the peptide primary structure on the titania precipitation activity at room temperature is not well understood. Through the selective binding of phage-displayed 12-mer peptides to TiO2 substrates, we have identified 20 peptides with an affinity for titania. The average numbers of arginine, lysine, and histidine residues present in these 20 peptides were distinctly higher than for the overall peptide-bearing phage library. Synthetic 16-mer versions of four of these peptides (i.e., 12-mer peptides with C-terminal tetrapeptide tags for quantitative spectrophotometry) induced the formation of 8.1–38.7 mol TiO2/mol peptide after exposure for only 10 min to an otherwise water-stable Ti(IV) complex at room temperature and a pH of 6.3. X-ray diffraction analyses, electron diffraction analyses, and high-resolution transmission electron microscopy revealed that the peptide-induced titania contained fine (2 nanocrystals, along with an amorphous phase. The titania yield increased with the number of positive charges carried by these peptides. On the basis of these results, a peptide was designed that exhibited the highest titania formation activity reported to date for a peptide (82.9 mol TiO2/mol peptide), as well as a reduced pH dependence for such titania formation

Protein-Mediated Layer-by-Layer Syntheses of Freestanding Microscale Titania Structures with Biologically Assembled 3-D Morphologies

A simple protein-mediated approach for preparing freestanding (silica free) microscale titania structures with morphologies inherited from complex-shaped, three-dimensional (3-D) biosilica templates (diatom frustules) is demonstrated. The silica diatom frustules were exposed in a repetitive alternating fashion to a silica-binding, titania-forming protein (protamine) and then to an aqueous titania precursor to build up a conformal titania-bearing coating. After organic pyrolysis at 500 °C, the conformal, continuous nature of the resulting crystalline anatase titania coating was confirmed by (i) demonstrating that a titania-coated frustule acted as a sensitive electrochemical hydrogen detector and (ii) selectively removing the silica templates to yield freestanding titania structures that retained the 3-D diatom frustule shape

High-Energy-Density Sol–Gel Thin Film Based on Neat 2‑Cyanoethyltrimethoxysilane

Hybrid organic–inorganic sol–gel dielectric thin films from a neat 2-cyanoethyltrimethoxysilane (CNETMS) precursor have been fabricated and their permittivity, dielectric strength, and energy density characterized. CNETMS sol–gel films possess compact, polar cyanoethyl groups and exhibit a relative permittivity of 20 at 1 kHz and breakdown strengths ranging from 650 V/μm to 250 V/μm for film thicknesses of 1.3 to 3.5 μm. Capacitors based on CNETMS films exhibit extractable energy densities of 7 J/cm³ at 300 V/μm, as determined by charge–discharge and polarization-electric field measurements, as well as an energy extraction efficiency of ∼91%. The large extractable energy resulting from the linear dielectric polarization behavior suggests that CNETMS films are promising sol–gel materials for pulsed power applications

Table1_Complex Age- and Cancer-Related Changes in Human Blood Transcriptome—Implications for Pan-Cancer Diagnostics.XLSX

Early cancer detection is the key to a positive clinical outcome. While a number of early diagnostics methods exist in clinics today, they tend to be invasive and limited to a few cancer types. Thus, a clear need exists for non-invasive diagnostics methods that can be used to detect the presence of cancer of any type. Liquid biopsy based on analysis of molecular components of peripheral blood has shown significant promise in such pan-cancer diagnostics; however, existing methods based on this approach require improvements, especially in sensitivity of early-stage cancer detection. The improvement would likely require diagnostics assays based on multiple different types of biomarkers and, thus, calls for identification of novel types of cancer-related biomarkers that can be used in liquid biopsy. Whole-blood transcriptome, especially its non-coding component, represents an obvious yet under-explored biomarker for pan-cancer detection. In this study, we show that whole transcriptome analysis using RNA-seq could indeed serve as a viable biomarker for pan-cancer detection. Furthermore, a class of long non-coding (lnc) RNAs, very long intergenic non-coding (vlinc) RNAs, demonstrated superior performance compared with protein-coding mRNAs. Finally, we show that age and presence of non-blood cancers change transcriptome in similar, yet not identical, directions and explore implications of this observation for pan-cancer diagnostics.</p

Table4_Complex Age- and Cancer-Related Changes in Human Blood Transcriptome—Implications for Pan-Cancer Diagnostics.XLSX

Early cancer detection is the key to a positive clinical outcome. While a number of early diagnostics methods exist in clinics today, they tend to be invasive and limited to a few cancer types. Thus, a clear need exists for non-invasive diagnostics methods that can be used to detect the presence of cancer of any type. Liquid biopsy based on analysis of molecular components of peripheral blood has shown significant promise in such pan-cancer diagnostics; however, existing methods based on this approach require improvements, especially in sensitivity of early-stage cancer detection. The improvement would likely require diagnostics assays based on multiple different types of biomarkers and, thus, calls for identification of novel types of cancer-related biomarkers that can be used in liquid biopsy. Whole-blood transcriptome, especially its non-coding component, represents an obvious yet under-explored biomarker for pan-cancer detection. In this study, we show that whole transcriptome analysis using RNA-seq could indeed serve as a viable biomarker for pan-cancer detection. Furthermore, a class of long non-coding (lnc) RNAs, very long intergenic non-coding (vlinc) RNAs, demonstrated superior performance compared with protein-coding mRNAs. Finally, we show that age and presence of non-blood cancers change transcriptome in similar, yet not identical, directions and explore implications of this observation for pan-cancer diagnostics.</p

DataSheet1_Complex Age- and Cancer-Related Changes in Human Blood Transcriptome—Implications for Pan-Cancer Diagnostics.pdf

Early cancer detection is the key to a positive clinical outcome. While a number of early diagnostics methods exist in clinics today, they tend to be invasive and limited to a few cancer types. Thus, a clear need exists for non-invasive diagnostics methods that can be used to detect the presence of cancer of any type. Liquid biopsy based on analysis of molecular components of peripheral blood has shown significant promise in such pan-cancer diagnostics; however, existing methods based on this approach require improvements, especially in sensitivity of early-stage cancer detection. The improvement would likely require diagnostics assays based on multiple different types of biomarkers and, thus, calls for identification of novel types of cancer-related biomarkers that can be used in liquid biopsy. Whole-blood transcriptome, especially its non-coding component, represents an obvious yet under-explored biomarker for pan-cancer detection. In this study, we show that whole transcriptome analysis using RNA-seq could indeed serve as a viable biomarker for pan-cancer detection. Furthermore, a class of long non-coding (lnc) RNAs, very long intergenic non-coding (vlinc) RNAs, demonstrated superior performance compared with protein-coding mRNAs. Finally, we show that age and presence of non-blood cancers change transcriptome in similar, yet not identical, directions and explore implications of this observation for pan-cancer diagnostics.</p