An enantioselective total synthesis of plagiochianin B is described that employs (+)-3-carene as its point of departure and delivers the enantiomer of the natural product. Key features of the ...synthesis include a palladium-mediated regioselective oxidative cleavage of an olefin residing on a pyridine derived from a 6π-azatriene electrocyclization.
Protein phosphorylation is an important post-translational modification that is an integral part of cellular function. The O-phosphorylated amino-acid residues, such as phosphoserine (pSer), ...phosphothreonine (pThr) and phosphotyrosine (pTyr), have dominated the literature while the acid labile N-linked phosphorylated amino acids, such as phosphohistidine (pHis), have largely been historically overlooked because of the acidic conditions routinely used in amino-acid detection and analysis. This review highlights some misinterpretations that have arisen in the existing literature, pinpoints outstanding questions and potential future directions to clarify the role of pHis in mammalian signalling systems. Particular emphasis is placed on pHis isomerization and the hybrid functionality for both pHis and pTyr of the proposed τ-pHis analogue bearing the triazole residue.
Purpose Following the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial, sorafenib has become the standard of care for patients with advanced unresectable hepatocellular ...carcinoma, but the relation between survival advantage and disease etiology remains unclear. To address this, we undertook an individual patient data meta-analysis of three large prospective randomized trials in which sorafenib was the control arm. Methods Of a total of 3,256 patients, 1,643 (50%) who received sorafenib were available. The primary end point was overall survival (OS). A Bayesian hierarchical approach for individual patient data meta-analyses was applied using a piecewise exponential model. Results are presented in terms of hazard ratios comparing sorafenib with alternative therapies according to hepatitis C virus (HCV) or hepatitis B virus (HBV) status. Results Hazard ratios show improved OS for sorafenib in patients who are both HBV negative and HCV positive (log hazard ratio, -0.27; 95% CI, -0.46 to -0.06). Median unadjusted survival is 12.6 (11.15 to 13.8) months for sorafenib and 10.2 (8.88 to 12.2) months for "other" treatments in this subgroup. There was no evidence of improvement in OS for any other patient subgroups defined by HBV and HCV. Results were consistent across all trials with heterogeneity assessed using Cochran's Q statistic. Conclusion There is consistent evidence that the effect of sorafenib on OS is dependent on patients' hepatitis status. There is an improved OS for patients negative for HBV and positive for HCV when treated with sorafenib. There was no evidence of any improvement in OS attributable to sorafenib for patients positive for HBV and negative for HCV.
This paper describes a data preprocessing algorithm that can be used to mitigate the effects of interfering spectral components when the goal is to detect the spectrum of unknown components in a ...mixture of known components or to verify the presence of suspected components in the spectrum of a mixture of known components. The algorithm is both relatively simple and applicable to a wide range of problems in spectroscopy. The range of applicability can be increased by combining the method with other data preprocessing methods, for example derivative spectra, and can also accommodate variability in the spectra of one or more of the known components. Examples of the application of the algorithm to real problems are given for near-infrared analysis of antibiotic drug formulations inside gelatin capsules and mid-infrared analysis of atmospheric pollutants.
Graphical Abstract
Herein, an efficient, scalable, and concise approach to an advanced pyrroloiminoquinone synthetic intermediate (6b) by way of a Larock indole synthesis is reported. The synthetic utility of this ...intermediate is demonstrated by its ready conversion to makaluvamines A (1) and K (4).
Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control of gene expression. Progress over ...recent years in determining the structures and activities of initiation factors, and in mapping their interactions in ribosomal initiation complexes, have advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity (which affects almost all scanning-dependent initiation) and through sequence-specific RNA-binding proteins and microRNAs (which affect individual mRNAs).
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A range of 7-oxo, 8-oxo, and 9-oxo amino acids, analogues of 8-oxo-2-aminodecanoic acid, one of the key components of the cyclic tetrapeptide apicidin, have been prepared by a three-step process ...involving copper-catalyzed allylation of serine-, aspartic acid-, and glutamic acid-derived organozinc reagents, followed by cross-metathesis of the resulting terminal alkenes with unsaturated ketones and hydrogenation. The intermediate 7-oxo-5-enones underwent a highly diastereoselective (dr ≥96:4) acid-catalyzed aza-Michael reaction to give trans-2,5-disubstituted pyrrolidines, 5-substituted proline derivatives. The aza-Michael reaction was first observed when the starting enones were allowed to stand in solution in deuterochloroform but can be efficiently promoted by catalytic amounts of dry HCl.
Optimal mobility, defined as relative ease and freedom of movement in all of its forms, is central to healthy aging. Mobility is a significant consideration for research, practice, and policy in ...aging and public health. We examined the public health burdens of mobility disability, with a particular focus on leading public health interventions to enhance walking and driving, and the challenges and opportunities for public health action. We propose an integrated mobility agenda, which draws on the lived experience of older adults. New strategies for research, practice, and policy are needed to move beyond categorical promotion programs in walking and driving to establish a comprehensive program to enhance safe mobility in all its forms.
We report the synthesis of a stable analogue of τ-phosphohistidine: 4-phosphopyrazol-2-yl alanine (pPza). Polyclonal antibodies generated against the mimic show high reactivity and selectivity for ...τ-phosphohistidine, with minor or no cross-reactivity towards non-phosphorylated histidine or O-phosphoamino acids, including phosphotyrosine.
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