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Current Opinion in Chemical Biology

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https://www.readbyqxmd.com/read/28628894/small-molecule-probes-for-cellular-death-machines
#1
REVIEW
Ying Li, Lihui Qian, Junying Yuan
The past decade has witnessed a significant expansion of our understanding about the regulated cell death mechanisms beyond apoptosis. The application of chemical biological approaches had played a major role in driving these exciting discoveries. The discovery and use of small molecule probes in cell death research has not only revealed significant insights into the regulatory mechanism of cell death but also provided new drug targets and lead drug candidates for developing therapeutics of human diseases with huge unmet need...
June 16, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28628856/mammalian-synthetic-biology-in-the-age-of-genome-editing-and-personalized-medicine
#2
REVIEW
Patrick Ho, Yvonne Y Chen
The recent expansion of molecular tool kits has propelled synthetic biology toward the design of increasingly sophisticated mammalian systems. Specifically, advances in genome editing, protein engineering, and circuitry design have enabled the programming of cells for diverse applications, including regenerative medicine and cancer immunotherapy. The ease with which molecular and cellular interactions can be harnessed promises to yield novel approaches to elucidate genetic interactions, program cellular functions, and design therapeutic interventions...
June 16, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28628855/progress-in-programming-spatiotemporal-patterns-and-machine-assembly-in-cell-free-protein-expression-systems
#3
REVIEW
Alexandra M Tayar, Shirley S Daube, Roy H Bar-Ziv
Building biological systems outside the cell is an emerging interdisciplinary research field aimed to study design principles, and to emulate biological functions for technology. Reconstructing programmable cellular functions, from assembly of protein/nucleic-acid machines to spatially distributed systems, requires implementing minimal systems of molecular interactions encoded in genes, source-sink protein expression dynamics, and materials platforms for reaction-diffusion scenarios. Here, we first review how molecular turnover mechanisms, combined with nonlinear interactions and feedback in cell-free gene networks enable programmable dynamic expression patterns in various compartments...
June 16, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28623730/quantitative-microscopy-based-on-single-molecule-fluorescence
#4
REVIEW
Seung-Ryoung Jung, Bryant S Fujimoto, Daniel T Chiu
Quantitative microscopy is needed to understand reactions or phenomena carried out by biological molecules such as enzymes, receptors, and membrane-localized proteins. Counting the biomolecules of interest in single organelles or cellular compartments is critical in these approaches. In this brief perspective, we focus on the development of quantitative fluorescence microscopies that measure the precise copy numbers of proteins in cellular organelles or purified samples. We introduce recent improvements in quantitative microscopies to overcome undercounting or overcounting errors in certain conditions...
June 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28623722/recent-advances-in-synthetic-biology-for-engineering-isoprenoid-production-in-yeast
#5
REVIEW
Claudia E Vickers, Thomas C Williams, Bingyin Peng, Joel Cherry
Isoprenoids (terpenes/terpenoids) have many useful industrial applications, but are often not produced at industrially viable level in their natural sources. Synthetic biology approaches have been used extensively to reconstruct metabolic pathways in tractable microbial hosts such as yeast and re-engineer pathways and networks to increase yields. Here we review recent advances in this field, focusing on central carbon metabolism engineering to increase precursor supply, re-directing carbon flux for production of C10, C15, or C20 isoprenoids, and chemical decoration of high value diterpenoids (C20)...
June 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28609710/sense-and-sensitivity-in-bioprocessing-detecting-cellular-metabolites-with-biosensors
#6
REVIEW
Linda Dekker, Karen M Polizzi
Biosensors use biological elements to detect or quantify an analyte of interest. In bioprocessing, biosensors are employed to monitor key metabolites. There are two main types: fully biological systems or biological recognition coupled with physical/chemical detection. New developments in chemical biosensors include multiplexed detection using microfluidics. Synthetic biology can be used to engineer new biological biosensors with improved characteristics. Although there have been few biosensors developed for bioprocessing thus far, emerging trends can be applied in the future...
June 10, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28609675/covalent-inhibitors-an-opportunity-for-rational-target-selectivity
#7
REVIEW
Roman Lagoutte, Remi Patouret, Nicolas Winssinger
There is a resurging interest in compounds that engage their target through covalent interactions. Cysteine's thiol is endowed with enhanced reactivity, making it the nucleophile of choice for covalent engagement with a ligand aligning an electrophilic trap with a cysteine residue in a target of interest. The paucity of cysteine in the proteome coupled to the fact that closely related proteins do not necessarily share a given cysteine residue enable a level of unprecedented rational target selectivity. The recent demonstration that a lysine's amine can also be engaged covalently with a mild electrophile extends the potential of covalent inhibitors...
June 10, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28605671/targeted-protein-knockdown-using-small-molecule-degraders
#8
REVIEW
Kanak Raina, Craig M Crews
Small molecule probes of biological systems have traditionally been designed to bind to and inhibit the active sites of their protein targets. While this class of pharmacological agents has been broadened by the development of a small number of allosteric and protein-protein interaction (PPI) inhibitors, conventional drug design still excludes 'undruggable' proteins that are neither enzymes nor receptors. Recent years have seen the emergence of new classes of small molecules that can target hitherto undruggable proteins by recruiting the cellular proteostasis machinery to selectively tag them for degradation...
June 9, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28578260/visualizing-glycans-on-single-cells-and-tissues-visualizing-glycans-on-single-cells-and-tissues
#9
REVIEW
Ben Ovryn, Jie Li, Senlian Hong, Peng Wu
Metabolic oligosaccharide engineering and chemoenzymatic glycan labeling have provided powerful tools to study glycans in living systems and tissue samples. In this review article, we summarize recent advances in this field with a focus on innovative approaches for glycan imaging. The presented applications demonstrate that several of the leading imaging methods, which have revolutionized quantitative cell biology, can be adapted to imaging glycans on single cells and tissues.
June 1, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28570865/cyclic-peptide-natural-products-chart-the-frontier-of-oral-bioavailability-in-the-pursuit-of-undruggable-targets
#10
REVIEW
Matthew R Naylor, Andrew T Bockus, Maria-Jesus Blanco, R Scott Lokey
As interest in protein-protein interactions and other previously-undruggable targets increases, medicinal chemists are returning to natural products for design inspiration toward molecules that transcend the paradigm of small molecule drugs. These compounds, especially peptides, often have poor ADME properties and thus require a more nuanced understanding of structure-property relationships to achieve desirable oral bioavailability. Although there have been few clinical successes in this chemical space to date, recent work has identified opportunities to introduce favorable physicochemical properties to peptidic macrocycles that maintain activity and oral bioavailability...
May 29, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28558293/blood-brain-barrier-peptide-shuttles
#11
REVIEW
Macarena Sánchez-Navarro, Ernest Giralt, Meritxell Teixidó
Brain delivery is hampered by the presence of the blood-brain barrier (BBB), a natural defence of the brain that protects it and allows the entrance of nutrients by several mechanisms. Taking advantage of these mechanisms is an opportunity to treat brain related diseases. Among the different alternatives, BBB peptide shuttles are gaining attention to increase brain delivery of therapeutics. The most recent advances in the field are analysed here.
May 27, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28544971/development-of-photostable-fluorophores-for-molecular-imaging
#12
REVIEW
Qinsi Zheng, Luke D Lavis
Advances in fluorescence microscopy promise to unlock details of biological systems with high spatiotemporal precision. These new techniques also place a heavy demand on the 'photon budget'-the number of photons one can extract from a sample. Improving the photostability of small molecule fluorophores using chemistry is a straightforward method for increasing the photon budget. Here, we review the (sometimes sparse) efforts to understand the mechanism of fluorophore photobleaching and recent advances to improve photostability through reducing the propensity for oxidation or through intramolecular triplet-state quenching...
May 22, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28544970/quantitative-chemical-imaging-with-stimulated-raman-scattering-microscopy
#13
REVIEW
Dan Fu
Chemical imaging plays an increasingly important role in studying heterogeneous biological systems. It combines molecular spectroscopy with high-resolution spatial information to create quantitative images of molecular distributions. Here I summarize recent progress in technical developments and biological applications of a specific chemical imaging technique-stimulated Raman scattering (SRS) microscopy. SRS microscopy allows for a wide range of molecules - both endogenous and exogenous - to be imaged at high spatial and temporal resolution in living cells, tissues, and organisms...
May 22, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28528024/structure-diverse-phylomer-libraries-as-a-rich-source-of-bioactive-hits-from-phenotypic-and-target-directed-screens-against-intracellular-proteins
#14
REVIEW
Paul M Watt, Nadia Milech, Shane R Stone
Phylomers are peptides derived from biodiverse protein fragments. Genetically encoded Phylomer libraries have been constructed, containing hundreds of billions of peptides derived from virtually all of the few thousand fold families found in the protein universe. They offer a rich source of high quality hits against diverse target sequences and have been used for three main purposes: firstly, to identify and validate targets in phenotypic screens; secondly, to block protein interactions with nanomolar potency binding affinities; thirdly as a source of more efficient cell penetrating peptides for the delivery of a wide range of biologics...
May 18, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28527906/fluorescent-probes-for-imaging-formaldehyde-in-biological-systems
#15
REVIEW
Kevin J Bruemmer, Thomas F Brewer, Christopher J Chang
Formaldehyde (FA) is a common environmental toxin but is also endogenously produced through a diverse array of essential biological processes, including mitochondrial one-carbon metabolism, metabolite oxidation, and nuclear epigenetic modifications. Its high electrophilicity enables reactivity with a wide variety of biological nucleophiles, which can be beneficial or detrimental to cellular function depending on the context. New methods that enable detection of FA in living systems can help disentangle the signal/stress dichotomy of this simplest reactive carbonyl species (RCS), and fluorescent probes for FA with high selectivity and sensitivity have emerged as promising chemical tools in this regard...
May 18, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28527344/harnessing-plant-metabolic-diversity
#16
REVIEW
Charlie Owen, Nicola J Patron, Ancheng Huang, Anne Osbourn
Advances in DNA sequencing and synthesis technologies in the twenty-first century are now making it possible to build large-scale pipelines for engineering plant natural product pathways into heterologous production species using synthetic biology approaches. The ability to decode the chemical potential of plants by sequencing their transcriptomes and/or genomes and to then use this information as an instruction manual to make drugs and other high-value chemicals is opening up new routes to harness the vast chemical diversity of the Plant Kingdom...
May 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28527343/engineering-genetically-encoded-tools-for-optogenetic-control-of-protein-activity
#17
REVIEW
Qi Liu, Chandra L Tucker
Optogenetic tools offer fast and reversible control of protein activity with subcellular spatial precision. In the past few years, remarkable progress has been made in engineering photoactivatable systems regulating the activity of cellular proteins. In this review, we discuss general strategies in designing and optimizing such optogenetic tools and highlight recent advances in the field, with specific focus on applications regulating protein catalytic activity.
May 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28521258/synchrotron-based-x-ray-microscopy-for-sub-100nm-resolution-cell-imaging
#18
REVIEW
Ying Zhu, Jichao Zhang, Aiguo Li, Yuanqing Zhang, Chunhai Fan
Microscopic imaging provides a straightforward approach to deepen our understanding of cellular events. While the resolution of optical microscopes is generally limited to 200-300nm due to the diffraction limit, there has been ever growing interest in studying cells at the sub-100nm regime. By exploiting the short wavelength, long penetration depth and elemental specificity of X-rays, synchrotron-based X-ray microscopy (XRM) has demonstrated its power in exploring the structure and function of cells at the nanometer resolution...
May 15, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28494316/combinatorial-chemistry-in-drug-discovery
#19
REVIEW
Ruiwu Liu, Xiaocen Li, Kit S Lam
Several combinatorial methods have been developed to create focused or diverse chemical libraries with a wide range of linear or macrocyclic chemical molecules: peptides, non-peptide oligomers, peptidomimetics, small-molecules, and natural product-like organic molecules. Each combinatorial approach has its own unique high-throughput screening and encoding strategy. In this article, we provide a brief overview of combinatorial chemistry in drug discovery with emphasis on recently developed new technologies for design, synthesis, screening and decoding of combinatorial library...
May 8, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28478369/designer-probiotics-for-the-prevention-and-treatment-of-human-diseases
#20
REVIEW
Koon Jiew Chua, Wee Chiew Kwok, Nikhil Aggarwal, Tao Sun, Matthew Wook Chang
Various studies have shown the beneficial effects of probiotics in humans. The use of synthetic biology to engineer programmable probiotics that specifically targets cancer, infectious agents, or other metabolic diseases has gained much interest since the last decade. Developments made in synthetic probiotics as therapeutics within the last three years will be discussed in this review.
May 4, 2017: Current Opinion in Chemical Biology
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