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Current Opinion in Chemical Biology

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28463802/a-three-step-framework-for-programming-pattern-formation
#8
REVIEW
Natalie S Scholes, Mark Isalan
The spatial organisation of gene expression is essential to create structure and function in multicellular organisms during developmental processes. Such organisation occurs by the execution of algorithmic functions, leading to patterns within a given domain, such as a tissue. Engineering these processes has become increasingly important because bioengineers are seeking to develop tissues ex vivo. Moreover, although there are several theories on how pattern formation can occur in vivo, the biological relevance and biotechnological potential of each of these remains unclear...
April 29, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28460291/voltage-imaging-with-genetically-encoded-indicators
#9
REVIEW
Yongxian Xu, Peng Zou, Adam E Cohen
Membrane voltages are ubiquitous throughout cell biology. Voltage is most commonly associated with excitable cells such as neurons and cardiomyocytes, although many other cell types and organelles also support electrical signaling. Voltage imaging in vivo would offer unique capabilities in reporting the spatial pattern and temporal dynamics of electrical signaling at the cellular and circuit levels. Voltage is not directly visible, and so a longstanding challenge has been to develop genetically encoded fluorescent voltage indicator proteins...
April 28, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28426952/plant-viruses-and-bacteriophages-for-drug-delivery-in-medicine-and-biotechnology
#10
REVIEW
Anna E Czapar, Nicole F Steinmetz
There are a wide variety of synthetic and naturally occurring nanomaterials under development for nanoscale cargo-delivery applications. Viruses play a special role in these developments, because they can be regarded as naturally occurring nanomaterials evolved to package and deliver cargos. While any nanomaterial has its advantage and disadvantages, viral nanoparticles (VNPs), in particular the ones derived from plant viruses and bacteriophages, are attractive options for cargo-delivery as they are biocompatible, biodegradable, and non-infectious to mammals...
April 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28412597/peptide-blockers-of-kv1-3-channels-in-t-cells-as-therapeutics-for-autoimmune-disease
#11
REVIEW
K George Chandy, Raymond S Norton
The voltage-gated Kv1.3 channel in T lymphocytes is a validated therapeutic target for diverse autoimmune diseases. Here we review the discovery of Kv1.3, its physiological role in T cells, and why it is an attractive target for modulating autoimmune responses. We focus on peptide inhibitors because the first Kv1.3-selective inhibitor in human trials is a peptide derived from a marine organism. Two broad classes of peptides block Kv1.3, the first from scorpions and the second from sea anemones. We describe their structures, their binding site in the external vestibule of Kv1...
April 13, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28399505/host-defense-antimicrobial-peptides-as-antibiotics-design-and-application-strategies
#12
REVIEW
Biswajit Mishra, Scott Reiling, D Zarena, Guangshun Wang
This review deals with the design and application strategies of new antibiotics based on naturally occurring antimicrobial peptides (AMPs). The initial candidate can be designed based on three-dimensional structure or selected from a library of peptides from natural or laboratory sources followed by optimization via structure-activity relationship studies. There are also advanced application strategies such as induction of AMP expression from host cells by various factors (e.g., metals, amino acids, vitamin D and sunlight), the use of engineered probiotic bacteria to deliver peptides, the design of prodrug and peptide conjugates to improve specific targeting...
April 8, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28388463/targeting-intracellular-protein-protein-interactions-with-cell-permeable-cyclic-peptides
#13
REVIEW
Ziqing Qian, Patrick G Dougherty, Dehua Pei
Intracellular protein-protein interactions (PPIs) are challenging targets for conventional drug modalities, because small molecules generally do not bind to their large, flat binding sites with high affinity, whereas monoclonal antibodies cannot cross the cell membrane to reach the targets. Cyclic peptides in the 700-2000 molecular-weight range have the sufficient size and a balanced conformational flexibility/rigidity for binding to flat PPI interfaces with antibody-like affinity and specificity. Several powerful cyclic peptide library technologies were developed over the past decade to rapidly discover potent, specific cyclic peptide ligands against proteins of interest including those involved in PPIs...
April 4, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28376346/progress-and-challenges-in-the-optimization-of-toxin-peptides-for-development-as-pain-therapeutics
#14
REVIEW
Chawita Netirojjanakul, Les P Miranda
The number of new toxin peptide discoveries has been rapidly growing in the past few decades. Because of progress in proteomics, sequencing technologies, and high throughput bioassays, the search for new toxin peptides from venom collections and potency optimization has become manageable. However, to date, only six toxin peptide-derived therapeutics have been approved by the USFDA, with only one, ziconotide, for a pain indication. The challenge of venom-derived peptide therapeutic development remains in improving selectivity to the target and more importantly, in delivery of these peptides to the sites of action in the central and peripheral nervous system...
April 1, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28371692/targeting-ligand-receptor-interactions-for-development-of-cancer-therapeutics
#15
REVIEW
Jun Woo Kim, Jennifer R Cochran
The biological importance and druggable properties of receptors and their cognate ligands have designated them as especially useful clinical targets. This significance continues to expand as new molecular insights underlying disease pathophysiology are uncovered. While both ligands and receptors have been exploited as drug targets, their differing biochemical properties require nuanced considerations for drug development, including where in the body they are located and how they are regulated on a cellular and molecular level...
March 31, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28319812/exploring-sequence-space-harnessing-chemical-and-biological-diversity-towards-new-peptide-leads
#16
REVIEW
Richard Obexer, Louise J Walport, Hiroaki Suga
From their early roots in natural products, peptides now represent an expanding class of novel drugs. Their modular structures make them ideal candidates for pooled library screening approaches. Key technologies for library generation and screening, such as SICLOPPS, phage display and mRNA display, give unparalleled access to tight binding peptides. Through combination with genetic code reprogramming and chemical modifications, access to more natural product-like libraries, spanning non-canonical peptide space, is readily achievable...
March 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28319811/protein-epitope-mimetic-macrocycles-as-biopharmaceuticals
#17
REVIEW
Anatol Luther, Kerstin Moehle, Eric Chevalier, Glenn Dale, Daniel Obrecht
Fully synthetic medium-sized macrocyclic peptides mimicking the key β-hairpin and α-helical protein epitopes relevant in many protein-protein interactions have emerged as a novel class of drugs with the potential to fill an important gap between small molecules and proteins. Conformationally stabilized macrocyclic scaffolds represent ideal templates for medicinal chemists to incorporate bioactive peptide and protein pharmacophores in order to generate novel drugs to treat diseases with high unmet medical need...
March 5, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28260651/ribosomally-synthesized-and-post-translationally-modified-peptide-natural-product-discovery-in-the-genomic-era
#18
REVIEW
Kenton J Hetrick, Wilfred A van der Donk
In the past 15 years, the cost of sequencing a genome has plummeted. Consequently, the number of sequenced bacterial genomes has exponentially increased, and methods for natural product discovery have evolved rapidly to take advantage of the wealth of genomic data. This review highlights applications of genome mining software to compare and organize large-scale data sets and methods for identifying unique biosynthetic pathways amongst the thousands of ribosomally synthesized and post-translationally modified peptide (RiPP) gene clusters...
March 2, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28258013/siclopps-cyclic-peptide-libraries-in-drug-discovery
#19
REVIEW
Ali Tavassoli
Cyclic peptide libraries have demonstrated significant potential when employed against challenging targets such as protein-protein interactions. While a variety of methods for library generation exist, genetically encoded libraries hold several advantages over their chemically synthesized counterparts; they are more readily accessible and allow straightforward hit deconvolution. One method for the intracellular generation of such libraries is split-intein circular ligation of peptides and proteins (SICLOPPS)...
February 28, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28249194/cyclotides-as-drug-design-scaffolds
#20
REVIEW
David J Craik, Junqiao Du
Cyclotides are ultra-stable peptides derived from plants. They are around 30 amino acids in size and are characterized by their head-to-tail cyclic backbone and cystine knot. Their exceptional stability and tolerance to sequence substitutions has led to their use as frameworks in drug design. This article describes recent developments in this field, particularly developments over the last two years relating to the grafting of bioactive peptide sequences into the cyclic cystine knot framework of cyclotides to stabilize the sequences...
February 26, 2017: Current Opinion in Chemical Biology
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