Diazo groups endure metabolism and enable chemoselectivity in cellulo.
Ontology highlight
ABSTRACT:
SUBMITTER: Andersen KA
PROVIDER: S-EPMC4372190 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Like azides, diazoacetamides undergo 1,3-dipolar cycloadditions with oxanorbornadienes (OND) in a reaction that is accelerated by the relief of strain in the transition state. The cycloaddition of a diazoacetamide with unstrained ethyl 4,4,4-trifluoro-2-butynoate is, however, 35-fold faster than with the analogous OND because of favorable interactions with the fluoro groups. Its rate constant (k = 0.53 M(-1) s(-1) in methanol) is comparable to those of strain-promoted azide-cyclooctyne cycloadditions.
| S-EPMC5148626 | biostudies-literature
Project description:Viruses are a significant threat to both human health and the economy, and there is an urgent need for novel anti-viral drugs and vaccines. High-resolution viral structures inform our understanding of the virosphere, and inspire novel therapies. Here we present a method of obtaining such structural information that avoids potentially disruptive handling, by collecting diffraction data from intact infected cells. We identify a suitable combination of cell type and virus to accumulate particles in the cells, establish a suitable time point where most cells contain virus condensates and use electron microscopy to demonstrate that these are ordered crystalline arrays of empty capsids. We then use an X-ray free electron laser to provide extremely bright illumination of sub-micron intracellular condensates of bacteriophage phiX174 inside living Escherichia coli at room temperature. We have been able to collect low resolution diffraction data. Despite the limited resolution and completeness of these initial data, due to a far from optimal experimental setup, we have used novel methodology to determine a putative space group, unit cell dimensions, particle packing and likely maturation state of the particles.
| S-EPMC5830620 | biostudies-literature
Project description:Efforts to trap early intermediates of the gold-catalyzed phenol synthesis failed. Neither inter- nor intramolecularly offered vinyl groups, ketones or alcohols were able to intercept the gold carbenoid species. This indicates that the competing steps of the gold-catalyzed phenol synthesis are much faster than the steps of the interception reaction. In the latter the barrier of activation is higher. At the same time this explains the high tolerance of this very efficient and general reaction towards functional groups.
| S-EPMC3135103 | biostudies-literature
Project description:The formation of C-Br(s) is one of the most fundamental reactions in organic synthesis. Oxidative bromination is a "green" way to achieve it. Aerobic bromination has drawn great interest in the past decades, while the poor substrate scope and selectivity, low efficiency, and the use of metal catalyst still confine its application. In this article, we establish a transition-metal-free aerobic bromination promoted by ionic liquid in a catalytic amount with controllable chemoselectivity toward numbers of C-Br(s) formed, and both NaBr/AcOH and HBr(aq) could be used as the bromine source. This methodology shows high efficiency and has a broad substrate scope for various kinds of C-H(s). We also validate this system by the gram-scale (one-pot) synthesis of functional molecules and direct recycle of the catalyst. The possible radical pathway of this catalysis is also presented with evidence.
| S-EPMC10785634 | biostudies-literature
Project description:Diazo-based precursors of photolabile groups have been used extensively for modifying nucleic acids, with the intention of toggling biological processes with light. These processes include transcription, translation and RNA interference. In these cases, the photolabile groups have been typically depicted as modifying the phosphate backbone of RNA and DNA. In this work we find that these diazo-based reagents in fact react very poorly with backbone phosphates. Instead, they show a remarkable specificity for terminal phosphates and very modest modification of the nucleobases. Furthermore, the photo deprotection of these terminal modifications is shown to be much more facile than nucleobase modified sites. In this study we have characterized this regiospecificity using RNA duplexes and model nucleotides, analyzed using LC/MS/MS. We have also applied this understanding of the regio-specificity to our technique of light activated RNA interference (LARI). We examined 27-mer double-stranded precursors of siRNA ('dsRNA'), and have modified them using the photo-cleavable di-methoxy nitro phenyl ethyl group (DMNPE) group. By incorporating terminal phosphates in the dsRNA, we are able to guide DMNPE to react at these terminal locations. These modified dsRNA duplexes show superior performance to our previously described DMNPE-modified siRNA, with the range of expression that can be toggled by light increasing by a factor of two.
| S-EPMC2715251 | biostudies-literature
Project description:The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signaling provides the cellular building blocks required for rapid growth. Here, we report that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 develop enlarged livers and are prone to liver tumor formation. Transcriptomic profiling reveals that Yap1 reprograms genes involved in glutamine metabolism. Analysis of gene expression in WT and lf:Yap transgenic zebrafish livers.
2016-08-02 | E-GEOD-82246 | biostudies-arrayexpress
Project description:The ability to selectively react one functional group in the presence of another underpins efficient reaction sequences. Despite many designer catalytic systems being reported for hydroboration reactions, which allow introduction of a functional handle for cross-coupling or act as mild method for reducing polar functionality, these platforms rarely deal with more complex systems where multiple potentially reactive sites exist. Here we demonstrate, for the first time, the ability to use light to distinguish between ketones and carboxylic acids in more complex molecules. By taking advantage of different activation modes, a single catalytic system can be used for hydroboration, with the chemoselectivity dictated only by the presence or absence of visible light.
| S-EPMC9305532 | biostudies-literature
Project description:Normal aging involves changes in the ability to acquire, consolidate and recall new information. It has been recently proposed that the reconsolidation process is also affected in older adults. Reconsolidation is triggered after reminder presentation, allowing memories to be modified: they can be impaired, strengthened or changed in their content. In young adults it was previously shown that the presentation of repetitive reminders induces memory strengthening one day after reactivation and the presentation of at least one reminder increases memory persistence several days after reactivation. However, until now this process has remained elusive in older adults. We hypothesize that older adults need a stronger reminder to induce memory strengthening through the reconsolidation process than young adults. To test this, we perform a three-day experiment. On day 1, participants learned 15 sound-word associations, on day 2 they received no reminders (NR group), one reminder (R group) or two rounds of reactivations (Rx2 group). Finally, they were tested on day 7. We found that, contrary to our hypothesis, older adults show a memory improvement triggered by repeated labilization/reconsolidation processes to an equal extent than young adults. These results open new perspectives into the use of reconsolidation to improve daily acquired information and the development of therapeutic home used tools to produce memory enhancement in healthy older adults or those with cognitive decline.
| S-EPMC7413497 | biostudies-literature
Project description:ObjectiveThe Psychotherapies for Chronic PTSD randomised trial found that three 14-week psychotherapies acutely benefitted patients with chronic posttraumatic stress disorder (PTSD). Previous research has reported sustained follow-up benefits for prolonged exposure (PE) and relaxation therapy (RT), but few comparable data exist for interpersonal psychotherapy (IPT). We describe 3-month follow-up for acute responders to all 3 treatments.MethodAcute responders, defined a priori as ≥30% improved from baseline, were reevaluated after 3-month no-treatment follow-up by independent evaluators using the Clinician-Administered PTSD Scale (CAPS).ResultsFifty of 110 initial study entrants met acute responder status at week 14. Forty-three (86%) responders entered follow-up: 23 remitters (CAPS ≤20) and 20 responders. At week 26, 27 had achieved remission status, 10 remained responders, and 6 had relapsed. Of week 14 remitters, 8 of 9 PE, all 8 IPT, and 4 of 6 RT patients remained remitted. Relapse rates were 7% (1/9) for PE, 10% (2/20) for IPT, and 33% (3/9) for RT. At week 26, PE showed greater improvement on CAPS than RT ( P = 0.048) and a trend for superiority over IPT ( P = 0.098), with no significant difference between IPT and RT. Depressive symptoms remained low during follow-up.ConclusionsThese are the first systematic data on follow-up responder status and persistence of acute treatment benefits in patients receiving individual IPT for chronic PTSD. Patients generally maintained gains across treatments, fluctuating most in RT. Study limitations include small sample size and brief follow-up interval. PTSD research should employ response and remission criteria.
| S-EPMC5788122 | biostudies-literature
Project description:Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions. These patterns are indicative of conserved selection pressures, but cannot be fully explained by known oncogenes and tumor suppressor genes. Using integrative analysis of CNA data from patient tumors and experimental systems, we report that principal component analysis-defined CNA signatures are predictive of glycolytic phenotypes, including FDG-avidity of patient tumors, and increased proliferation. The primary glycolysis-linked CNA signature is associated with p53 mutation and shows coordinate amplification of glycolytic genes and other cancer-linked metabolic enzymes including TIGAR and RPIA. In contrast, alternative signatures involve both different mechanisms of tumor suppression loss (eg, MDM2 amplification) and different glycolysis enzyme isoforms. Furthermore, a cross-species CNA comparison identified 21 conserved CNA regions, containing 13 enzymes in the glycolysis and pentose phosphate pathways in addition to known cancer driving genes. In validation experiments, exogenous expression of hexokinase and enolase enzymes resulted in reduced propensities for amplifications at the corresponding endogenous loci. Our findings support metabolic stress as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution.
2017-02-14 | GSE63306 | GEO