The evolving capabilities of rhodopsin-based genetically encoded voltage indicators.
Abstract Protein engineering over the past four years has made rhodopsin-based genetically encoded voltage indicators a leading candidate to achieve the task of reporting action potentials from a population of genetically targeted neurons in vivo. Rational design and large-scale screening efforts have steadily improved the dynamic range and kinetics of the rhodopsin voltage-sensing domain, and coupling these rhodopsins to bright fluorescent proteins has supported bright fluorescence readout of the large and rapid rhodopsin voltage response. The rhodopsin-fluorescent protein fusions have the highest achieved signal...
Source: Current Opinion in Chemical Biology - July 1, 2015 Category: Biochemistry Authors: Gong Y Tags: Curr Opin Chem Biol Source Type: research

Folding and function in α/β-peptides: targets and therapeutic applications.
Folding and function in α/β-peptides: targets and therapeutic applications. Curr Opin Chem Biol. 2015 Jun 29;28:75-82 Authors: Werner HM, Horne WS Abstract Combining natural α-amino acid residues and unnatural β-amino acid residues in a single chain leads to heterogeneous-backbone oligomers called α/β-peptides. Despite their unnatural backbones, α/β-peptides can manifest a variety of folding patterns and biological functions reminiscent of natural peptides and proteins. Moreover, incorporation of β-residues can impart useful properties to the oligomer s...
Source: Current Opinion in Chemical Biology - June 29, 2015 Category: Biochemistry Authors: Werner HM, Horne WS Tags: Curr Opin Chem Biol Source Type: research

Enzymatic conversion of lignin into renewable chemicals.
Abstract The aromatic heteropolymer lignin is a major component of plant cell walls, and is produced industrially from paper/pulp manufacture and cellulosic bioethanol production. Conversion of lignin into renewable chemicals is a major unsolved problem in the development of a biomass-based biorefinery. The review describes recent developments in the understanding of bacterial enzymes for lignin breakdown, such as DyP peroxidases, bacterial laccases, and beta-etherase enzymes. The use of pathway engineering methods to construct genetically modified microbes to convert lignin to renewable chemicals (e.g. vanillin, ...
Source: Current Opinion in Chemical Biology - June 25, 2015 Category: Biochemistry Authors: Bugg TD, Rahmanpour R Tags: Curr Opin Chem Biol Source Type: research

Homogeneously modified immunoglobulin domains for therapeutic application.
Abstract The field of therapeutic antibodies has been revolutionized over the past decade, led by the development of novel antibody-modification technologies. Besides the huge success achieved by therapeutic monoclonal antibodies, a diversity of antibody derivatives have emerged with hope to outperform their parental antibodies. Here we review the recent development of methodologies to modify immunoglobulin domains and their therapeutic applications. The innovative genetic and chemical approaches enable novel and controllable modifications on immunoglobulin domains, producing homogeneous therapeutics with new func...
Source: Current Opinion in Chemical Biology - June 25, 2015 Category: Biochemistry Authors: Liu T, Du J, Luo X, Schultz PG, Wang F Tags: Curr Opin Chem Biol Source Type: research

Fluorescence imaging using synthetic GFP chromophores.
Abstract Green fluorescent protein and related proteins carry chromophores formed within the protein from their own amino acids. Corresponding synthetic compounds are non-fluorescent in solution due to photoinduced isomerization of the benzylideneimidiazolidinone core. Restriction of this internal rotation by binding to host molecules leads to pronounced, up to three orders of magnitude, increase of fluorescence intensity. This property allows using GFP chromophore analogs as fluorogenic dyes to detect metal ions, proteins, nucleic acids, and other hosts. For example, RNA aptamer named Spinach, which binds to and ...
Source: Current Opinion in Chemical Biology - June 24, 2015 Category: Biochemistry Authors: Walker CL, Lukyanov KA, Yampolsky IV, Mishin AS, Bommarius AS, Duraj-Thatte AM, Azizi B, Tolbert LM, Solntsev KM Tags: Curr Opin Chem Biol Source Type: research

Near-infrared fluorescent proteins engineered from bacterial phytochromes.
We describe phenotypes of NIR FPs and their photochemical and intracellular properties. We discuss NIR FP applications for imaging of various cell types, tissues and animal models in basic and translational research. In this discussion, we focus on NIR FPs that efficiently incorporate endogenous biliverdin chromophore and therefore can be used as straightforward as GFP-like proteins. We also overview a usage of NIR FPs in different imaging platforms, from planar epifluorescence to tomographic and photoacoustic technologies. PMID: 26115447 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - June 23, 2015 Category: Biochemistry Authors: Shcherbakova DM, Baloban M, Verkhusha VV Tags: Curr Opin Chem Biol Source Type: research

Genetically encoded voltage indicators for large scale cortical imaging come of age.
g C Abstract Electrical signals are fundamental to cellular sensing, communication and motility. In the nervous system, information is represented as receptor, synaptic and action potentials. Understanding how brain functions emerge from these electrical signals is one of the ultimate challenges in neuroscience and requires a methodology to monitor membrane voltage transients from large numbers of cells at high spatio-temporal resolution. Optical voltage imaging holds longstanding promises to achieve this, and has gained a fresh powerful momentum with the development of genetically encoded voltage indicators (GEVI...
Source: Current Opinion in Chemical Biology - June 23, 2015 Category: Biochemistry Authors: Knöpfel T, Gallero-Salas Y, Song C Tags: Curr Opin Chem Biol Source Type: research

Rational design and evolutional fine tuning of Saccharomyces cerevisiae for biomass breakdown.
Abstract Conferring biomass hydrolysis activity on yeast through genetic engineering has paved the way for the development of groundbreaking processes for producing liquid fuels and commodity chemicals from lignocellulosic biomass. However, the overproduction and misfolding of heterologous and endogenous proteins can trigger cellular stress, increasing the metabolic burden and retarding growth. Improving the efficiency of lignocellulosic breakdown requires engineering of yeast secretory pathway based on system-wide metabolic analysis as well as DNA constructs for enhanced cellulase gene expression with advanced mo...
Source: Current Opinion in Chemical Biology - June 22, 2015 Category: Biochemistry Authors: Hasunuma T, Ishii J, Kondo A Tags: Curr Opin Chem Biol Source Type: research

A renaissance in RNA synthetic biology: new mechanisms, applications and tools for the future.
Abstract Since our ability to engineer biological systems is directly related to our ability to control gene expression, a central focus of synthetic biology has been to develop programmable genetic regulatory systems. Researchers are increasingly turning to RNA regulators for this task because of their versatility, and the emergence of new powerful RNA design principles. Here we review advances that are transforming the way we use RNAs to engineer biological systems. First, we examine new designable RNA mechanisms that are enabling large libraries of regulators with protein-like dynamic ranges. Next, we review em...
Source: Current Opinion in Chemical Biology - June 18, 2015 Category: Biochemistry Authors: Chappell J, Watters KE, Takahashi MK, Lucks JB Tags: Curr Opin Chem Biol Source Type: research

Recent progress in luminescent proteins development.
Abstract Bioimaging requires not only high sensitivity but also minimal invasiveness. Bioimaging using luminescent proteins is potentially free from problems such as photo-induced damage or an undesirable physical reaction to the sample, which are often caused by illumination with an external light required in fluorescence imaging. The recent development of several luminescent proteins and substrates have greatly improved the brightness of luminescence imaging, facilitating its application by many researchers. In this short review, we summarize recent advances in development of luminescent proteins, substrates, an...
Source: Current Opinion in Chemical Biology - June 18, 2015 Category: Biochemistry Authors: Saito K, Nagai T Tags: Curr Opin Chem Biol Source Type: research

Peeling away the layers of ubiquitin signaling complexities with synthetic ubiquitin-protein conjugates.
Abstract Covalent attachment of ubiquitin, a process termed ubiquitination, affects the location, function, and stability of modified proteins. Significant advances have been made in building synthetic ubiquitin-protein conjugates that can be used to investigate how ubiquitin regulates diverse biological processes. Herein we describe recent advances and discuss how chemical methods have been implemented to address the molecular underpinnings of ubiquitin-dependent cellular signaling. PMID: 26093241 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - June 17, 2015 Category: Biochemistry Authors: Pham GH, Strieter ER Tags: Curr Opin Chem Biol Source Type: research

LOV-based reporters for fluorescence imaging.
Abstract Chromophore-binding domains from plant and bacterial photoreceptor proteins have recently gathered increasing attention as new sources of genetically encoded fluorescent proteins (FPs). In particular, FPs based on the flavin-binding LOV (light, oxygen, or voltage sensing) domain offer advantages over green fluorescent protein (GFP) owing to their smaller size, pH and thermal stability, utility under anaerobic conditions and their ability to generate reactive oxygen species. This review focuses on the potential applications of this emerging class of fluorescent reporters, discusses the advantages and limit...
Source: Current Opinion in Chemical Biology - June 15, 2015 Category: Biochemistry Authors: Buckley AM, Petersen J, Roe AJ, Douce GR, Christie JM Tags: Curr Opin Chem Biol Source Type: research

Quantitative two-photon imaging of fluorescent biosensors.
Abstract Fluorescent biosensors are now routinely imaged using two-photon microscopy in intact tissue, for instance, in brain slices and brains in living animals. But most studies measure temporal variation-for example, calcium transients in response to neuronal activity-rather than calibrated levels of biosensor occupancy (and thus levels of the sensed analyte). True quantitative measurements are challenging, since it is difficult or impossible to calibrate a sensor's dose-response in situ, and difficult to compare the optical signals from tissue to those during in vitro calibration. Ratiometric measurements (at ...
Source: Current Opinion in Chemical Biology - June 12, 2015 Category: Biochemistry Authors: Yellen G, Mongeon R Tags: Curr Opin Chem Biol Source Type: research

Synthetic protein lipidation.
Abstract Fatty acylation of proteins is a versatile co-translational or post-translational modification that plays a key role in human physiology and disease. It is tightly controlled by a set of enzymes which catalyze the covalent attachment of fatty acids onto protein substrates, resulting in regulation of protein function, stability and interaction with other proteins or membranes. Some fatty acyltransferases have emerged to function as tumor suppressors or oncogenes, while others contribute to pathogenesis and neurodegenerative disorders. Yet our understanding of the molecular mechanism of action of these enzy...
Source: Current Opinion in Chemical Biology - June 12, 2015 Category: Biochemistry Authors: Hannoush RN Tags: Curr Opin Chem Biol Source Type: research

Designs and sensing mechanisms of genetically encoded fluorescent voltage indicators.
Abstract Neurons tightly regulate the electrical potential difference across the plasma membrane with millivolt accuracy and millisecond resolution. Membrane voltage dynamics underlie the generation of an impulse, the transduction of impulses from one end of the neuron to the other, and the release of neurotransmitters. Imaging these voltage dynamics in multiple neurons simultaneously is therefore crucial for understanding how neurons function together within circuits in intact brains. Genetically encoded fluorescent voltage sensors have long been desired to report voltage in defined subsets of neurons with optica...
Source: Current Opinion in Chemical Biology - June 11, 2015 Category: Biochemistry Authors: St-Pierre F, Chavarha M, Lin MZ Tags: Curr Opin Chem Biol Source Type: research

Dark dyes-bright complexes: fluorogenic protein labeling.
Abstract Complexes formed between organic dyes and genetically encoded proteins combine the advantages of stable and tunable fluorescent molecules and targetable, biologically integrated labels. To overcome the challenges imposed by labeling with bright fluorescent dyes, a number of approaches now exploit chemical or environmental changes to control the properties of a bound dye, converting dyes from a weakly fluorescent state to a bright, easily detectable complex. Optimized, such approaches avoid the need for removal of unbound dyes, facilitate rapid and simple assays in cultured cells and enable hybrid labeling...
Source: Current Opinion in Chemical Biology - June 5, 2015 Category: Biochemistry Authors: Bruchez MP Tags: Curr Opin Chem Biol Source Type: research

DNA nanotechnology: new adventures for an old warhorse.
Abstract As the blueprint of life, the natural exploits of DNA are admirable. However, DNA should not only be viewed within a biological context. It is an elegantly simple yet functionally complex chemical polymer with properties that make it an ideal platform for engineering new nanotechnologies. Rapidly advancing synthesis and sequencing technologies are enabling novel unnatural applications for DNA beyond the realm of genetics. Here we explore the chemical biology of DNA nanotechnology for emerging applications in communication and digital data storage. Early studies of DNA as an alternative to magnetic and opt...
Source: Current Opinion in Chemical Biology - June 5, 2015 Category: Biochemistry Authors: Zakeri B, Lu TK Tags: Curr Opin Chem Biol Source Type: research

Synthetic biology expands chemical control of microorganisms.
Abstract The tools of synthetic biology allow researchers to change the ways engineered organisms respond to chemical stimuli. Decades of basic biology research and new efforts in computational protein and RNA design have led to the development of small molecule sensors that can be used to alter organism function. These new functions leap beyond the natural propensities of the engineered organisms. They can range from simple fluorescence or growth reporting to pathogen killing, and can involve metabolic coordination among multiple cells or organisms. Herein, we discuss how synthetic biology alters microorganisms' ...
Source: Current Opinion in Chemical Biology - June 5, 2015 Category: Biochemistry Authors: Ford TJ, Silver PA Tags: Curr Opin Chem Biol Source Type: research

Novel theranostic agents for next-generation personalized medicine: small molecules, nanoparticles, and engineered mammalian cells.
Abstract Modern medicine is currently undergoing a paradigm shift from conventional disease treatments based on the diagnosis of a generalized disease state to a more personalized, customized treatment model based on molecular-level diagnosis. This uses novel biosensors that can precisely extract disease-related information from complex biological systems. Moreover, with the recent progress in chemical biology, materials science, and synthetic biology, it has become possible to simultaneously conduct diagnosis and targeted therapy (theranostics/theragnosis) by directly connecting the readout of a biosensor to a th...
Source: Current Opinion in Chemical Biology - June 5, 2015 Category: Biochemistry Authors: Kojima R, Aubel D, Fussenegger M Tags: Curr Opin Chem Biol Source Type: research

Development of biosensors and their application in metabolic engineering.
Abstract In a sustainable bioeconomy, many commodities and high value chemicals, including pharmaceuticals, will be manufactured using microbial cell factories from renewable feedstocks. These cell factories can be efficiently generated by constructing libraries of diversified genomes followed by screening for the desired phenotypes. However, methods available for microbial genome diversification far exceed our ability to screen and select for those variants with optimal performance. Genetically encoded biosensors have shown the potential to address this gap, given their ability to respond to small molecule bindin...
Source: Current Opinion in Chemical Biology - June 4, 2015 Category: Biochemistry Authors: Zhang J, Jensen MK, Keasling JD Tags: Curr Opin Chem Biol Source Type: research

Getting pumped: membrane efflux transporters for enhanced biomolecule production.
Abstract Small molecule production in microbial hosts is limited by the accumulation of the product inside the cell. Efflux transporters show promise as a solution to removal of the often-toxic products. Recent advances in transporter identification through expression profiling, heterologous expression, and knockout studies have identified transporters capable of secreting compounds of biotechnological interest. In addition, engineering of well-studied transporters has shown that substrate specificity in these transporters is malleable. Future work in identification, engineering, and expression of small molecule e...
Source: Current Opinion in Chemical Biology - June 4, 2015 Category: Biochemistry Authors: Boyarskiy S, Tullman-Ercek D Tags: Curr Opin Chem Biol Source Type: research

Emerging fluorescent protein technologies.
Abstract Fluorescent proteins (FPs), such as the Aequorea jellyfish green FP (GFP), are firmly established as fundamental tools that enable a wide variety of biological studies. Specifically, FPs can serve as versatile genetically encoded markers for tracking proteins, organelles, or whole cells, and as the basis for construction of biosensors that can be used to visualize a growing array of biochemical events in cells and tissues. In this review we will focus on emerging applications of FPs that represent unprecedented new directions for the field. These emerging applications include new strategies for using FPs ...
Source: Current Opinion in Chemical Biology - May 28, 2015 Category: Biochemistry Authors: Enterina JR, Wu L, Campbell RE Tags: Curr Opin Chem Biol Source Type: research

Novel uses of fluorescent proteins.
Abstract The field of genetically encoded fluorescent probes is developing rapidly. New chromophore structures were characterized in proteins of green fluorescent protein (GFP) family. A number of red fluorescent sensors, for example, for pH, Ca(2+) and H2O2, were engineered for multiparameter imaging. Progress in development of microscopy hardware and software together with specially designed FPs pushed superresolution fluorescence microscopy towards fast live-cell imaging. Deeper understanding of FPs structure and photophysics led to further development of imaging techniques. In addition to commonly used GFP-lik...
Source: Current Opinion in Chemical Biology - May 25, 2015 Category: Biochemistry Authors: Mishin AS, Belousov VV, Solntsev KM, Lukyanov KA Tags: Curr Opin Chem Biol Source Type: research

Increasing the delivery of next generation therapeutics from high throughput screening libraries.
Abstract The pharmaceutical industry has historically relied on high throughput screening as a cornerstone to identify chemical equity for drug discovery projects. However, with pharmaceutical companies moving through a phase of diminished returns and alternative hit identification strategies proving successful, it is more important than ever to understand how this approach can be used more effectively to increase the delivery of next generation therapeutics from high throughput screening libraries. There is a wide literature that describes HTS and fragment based screening approaches which offer clear direction on...
Source: Current Opinion in Chemical Biology - April 20, 2015 Category: Biochemistry Authors: Wigglesworth MJ, Murray DC, Blackett CJ, Kossenjans M, Nissink JW Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Next generation therapeutics: Creating and exploiting the chemistry of large numbers.
PMID: 25890575 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - April 15, 2015 Category: Biochemistry Authors: Scheuermann J, Neri D Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Bioinorganic chemistry: Bioinorganic catalysis for renewable energy.
PMID: 25791681 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - March 17, 2015 Category: Biochemistry Authors: Lim MH, Lu Y Tags: Curr Opin Chem Biol Source Type: research

Dual-pharmacophore DNA-encoded chemical libraries.
Abstract In contrast to single-pharmacophore DNA-encoded libraries, where only one chemical moiety is linked to DNA, dual-pharmacophore DNA-encoded chemical libraries feature the display of two independent small-molecules in close proximity. This, in principle, allows to explore adjacent epitopes on a pharmaceutical target of choice and hence the discovery of simultaneously binding pairs of fragments, by virtue of the chelate effect. PMID: 25779969 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - March 13, 2015 Category: Biochemistry Authors: Scheuermann J, Neri D Tags: Curr Opin Chem Biol Source Type: research

Encoded libraries of chemically modified peptides.
This article reviews the chemistry involved, the properties of the peptide ligands, and the new opportunities offered by chemical modification of DNA-encoded peptide libraries. PMID: 25768886 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - March 10, 2015 Category: Biochemistry Authors: Heinis C, Winter G Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Biocatalysis and biotransformation: Bio-inspired, bio-based and bio-linked catalysis.
r V PMID: 25765737 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - March 9, 2015 Category: Biochemistry Authors: Ward TR, Köhler V Tags: Curr Opin Chem Biol Source Type: research

Approaches to the design of catalytic metallodrugs.
Abstract Metal ions are known to act as catalytic centres in metallo-enzymes. On the other hand, low-molecular-weight metal complexes are widely used as catalysts in chemical systems. However, small catalysts do not have a large protein ligand to provide substrate selectivity and minimize catalyst poisoning. Despite the challenges that the lack of a protein ligand might pose, some success in the use of metal catalysts for biochemical transformations has been reported. Here, we present a brief overview of such reports, especially involving catalytic reactions in cells. Examples include CC bond formation, deprotecti...
Source: Current Opinion in Chemical Biology - March 9, 2015 Category: Biochemistry Authors: Soldevila-Barreda JJ, Sadler PJ Tags: Curr Opin Chem Biol Source Type: research

Elaboration of copper-oxygen mediated CH activation chemistry in consideration of future fuel and feedstock generation.
Abstract To contribute solutions to current energy concerns, improvements in the efficiency of dioxygen mediated CH bond cleavage chemistry, for example, selective oxidation of methane to methanol, could minimize losses in natural gas usage or produce feedstocks for fuels. Oxidative CH activation is also a component of polysaccharide degradation, potentially affording alternative biofuels from abundant biomass. Thus, an understanding of active-site chemistry in copper monooxygenases, those activating strong CH bonds is briefly reviewed. Then, recent advances in the synthesis-generation and study of various copper-...
Source: Current Opinion in Chemical Biology - March 7, 2015 Category: Biochemistry Authors: Lee JY, Karlin KD Tags: Curr Opin Chem Biol Source Type: research

Chemical ligation methods for the tagging of DNA-encoded chemical libraries.
Abstract The generation of DNA-encoded chemical libraries requires the unimolecular association of multiple encoding oligonucleotides with encoded chemical entities during combinatorial synthesis processes. This has traditionally been achieved using enzymatic ligation. We discuss a range of chemical ligation methods that provide alternatives to enzymatic ligation. These chemical ligation methods include the generation of modified internucleotide linkages that support polymerase translocation and other modified linkages that while not supporting the translocation of polymerases can also be used to generate individu...
Source: Current Opinion in Chemical Biology - March 7, 2015 Category: Biochemistry Authors: Keefe AD, Clark MA, Hupp CD, Litovchick A, Zhang Y Tags: Curr Opin Chem Biol Source Type: research

Fidelity by design: Yoctoreactor and binder trap enrichment for small-molecule DNA-encoded libraries and drug discovery.
Abstract DNA-encoded small-molecule library (DEL) technology allows vast drug-like small molecule libraries to be efficiently synthesized in a combinatorial fashion and screened in a single tube method for binding, with an assay readout empowered by advances in next generation sequencing technology. This approach has increasingly been applied as a viable technology for the identification of small-molecule modulators to protein targets and as precursors to drugs in the past decade. Several strategies for producing and for screening DELs have been devised by both academic and industrial institutions. This review hig...
Source: Current Opinion in Chemical Biology - February 27, 2015 Category: Biochemistry Authors: Blakskjaer P, Heitner T, Hansen NJ Tags: Curr Opin Chem Biol Source Type: research

Small targeted cytotoxics from DNA-encoded chemical libraries.
Abstract Conventional chemotherapeutic drugs do not selectively localize to tumors, causing undesired toxicities to healthy organs, and precluding the escalation to therapeutically active regimens. The selective delivery at sites of disease of potent effector molecules represents a promising strategy for the treatment of cancer and other diseases. High affinity antibodies towards disease-associated antigens are currently the vehicles of choice for the targeted delivery of payloads. Low molecular weight ligands have the potential to overcome some of the intrinsic limitations associated with antibodies, and have rec...
Source: Current Opinion in Chemical Biology - February 26, 2015 Category: Biochemistry Authors: Samain F, Casi G Tags: Curr Opin Chem Biol Source Type: research

Novel selection methods for DNA-encoded chemical libraries.
Abstract Driven by the need for new compounds to serve as biological probes and leads for therapeutic development and the growing accessibility of DNA technologies including high-throughput sequencing, many academic and industrial groups have begun to use DNA-encoded chemical libraries as a source of bioactive small molecules. In this review, we describe the technologies that have enabled the selection of compounds with desired activities from these libraries. These methods exploit the sensitivity of in vitro selection coupled with DNA amplification to overcome some of the limitations and costs associated with con...
Source: Current Opinion in Chemical Biology - February 24, 2015 Category: Biochemistry Authors: Chan AI, McGregor LM, Liu DR Tags: Curr Opin Chem Biol Source Type: research

Targeting carbonic anhydrase IX with small organic ligands.
Abstract Carbonic anhydrase IX (CAIX) is expressed in many solid tumors in response to hypoxia and plays an important role in tumor acid-base homeostasis under these conditions. It is also constitutively expressed in the majority of renal cell carcinoma. Its functional inhibition with small molecules has recently been shown to retard tumor growth in murine models of cancer, reduce metastasis and tumor stem cell expansion. Additionally, CAIX is a promising antigen for targeted drug delivery approaches. Initially validated with anti-CAIX antibodies, the tumor-homing capacity of high-affinity small-molecule ligands o...
Source: Current Opinion in Chemical Biology - February 23, 2015 Category: Biochemistry Authors: Wichert M, Krall N Tags: Curr Opin Chem Biol Source Type: research

DNA-encoded chemical libraries of macrocycles.
PMID: 25710630 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - February 21, 2015 Category: Biochemistry Authors: Connors WH, Hale SP, Terrett NK Tags: Curr Opin Chem Biol Source Type: research

Selection-based discovery of macrocyclic peptides for the next generation therapeutics.
Abstract Naturally occurring macrocyclic peptides represent a unique class of compounds that exhibit various biological activities ranging from antibiotics to immunosuppressant. Although the discovery of such macrocyclic peptides had relied on their isolation from living organisms, recent advances in ribosomal peptide synthesis and in display techniques made it possible to use artificially generated macrocyclic peptide libraries for selection of ligands for biologically relevant proteins. In this review, we discuss the technologies and their applications for the discovery of peptide ligands. PMID: 25703142 [P...
Source: Current Opinion in Chemical Biology - February 19, 2015 Category: Biochemistry Authors: Morioka T, Loik ND, Hipolito CJ, Goto Y, Suga H Tags: Curr Opin Chem Biol Source Type: research

High-valent metal-oxo intermediates in energy demanding processes: from dioxygen reduction to water splitting.
Abstract Four-electron reduction of dioxygen to water and splitting of water to dioxygen are extremely important processes in the context of attaining clean renewable energy sources. High-valent metal-oxo cores are proposed as reactive intermediates in these vital processes, although they have only been isolated in extremely rare cases in the biological systems thereby making the mechanism ambiguous. Recent biomimetic studies have, however, aided in our understanding of the fundamental reactivity of the high-valent metal-oxo species in various reactions relevant to energy conversion. All these studies are summariz...
Source: Current Opinion in Chemical Biology - February 18, 2015 Category: Biochemistry Authors: Ray K, Heims F, Schwalbe M, Nam W Tags: Curr Opin Chem Biol Source Type: research

Novel encoding methods for DNA-templated chemical libraries.
Abstract Among various types of DNA-encoded chemical libraries, DNA-templated library takes advantage of the sequence-specificity of DNA hybridization, enabling not only highly effective DNA-templated chemical reactions, but also high fidelity in library encoding. This brief review summarizes recent advances that have been made on the encoding strategies for DNA-templated libraries, and it also highlights their respective advantages and limitations for the preparation of DNA-encoded libraries. PMID: 25635927 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - January 27, 2015 Category: Biochemistry Authors: Li G, Zheng W, Liu Y, Li X Tags: Curr Opin Chem Biol Source Type: research

Identification of optimal protein binders through the use of large genetically encoded display libraries.
Abstract The use of large genetically encoded binder libraries in co-operation with display technologies has matured over the past 25 years, and is now one of the primary methods used for selection of protein binders. Display technology has proven to be a robust and versatile method for generating binders to almost any antigen of interest. The evolution of this technology beyond antibody phage display has opened up new aspects for the concept of designer biologics. The ability to construct large populations of eukaryotic cells, including mammalian cells, where each cell expresses an individual antibody, peptide or...
Source: Current Opinion in Chemical Biology - January 24, 2015 Category: Biochemistry Authors: McCafferty J, Schofield D Tags: Curr Opin Chem Biol Source Type: research

Solar-driven proton and carbon dioxide reduction to fuels - lessons from metalloenzymes.
Abstract Metalloenzymes such as hydrogenases and carbon monoxide dehydrogenase can be attached to light-harvesting agents to produce informative photocatalytic systems of varying intricacy. Systematic studies yield important insight into mechanistic and design principles of artificial photosynthesis - one route to future renewable energy conversion, and the unconventional experiments reveal interesting new criteria for the catalytic performance of metals in biology. Recent advances are interpreted in terms of the importance of enzyme active centres that have evolved to perform fast and efficient catalysis using ab...
Source: Current Opinion in Chemical Biology - January 23, 2015 Category: Biochemistry Authors: Bachmeier A, Armstrong F Tags: Curr Opin Chem Biol Source Type: research

Oxygen-evolving complex of Photosystem II: an analysis of second-shell residues and hydrogen-bonding networks.
Abstract The oxygen-evolving complex (OEC) is a Mn4O5Ca cluster embedded in the Photosystem II (PSII) protein complex. As the site of water oxidation, the OEC is connected to the lumen by channels that conduct water, oxygen, and/or protons during the catalytic cycle. The hydrogen-bond networks found in these channels also serve to stabilize the oxidized intermediates, known as the S states. We review recent developments in characterizing these networks via protein mutations, molecular inhibitors, and computational modeling. On the basis of these results, we highlight regions of the PSII protein in which changes ha...
Source: Current Opinion in Chemical Biology - January 23, 2015 Category: Biochemistry Authors: Vogt L, Vinyard DJ, Khan S, Brudvig GW Tags: Curr Opin Chem Biol Source Type: research

Selection of multiple agonist antibodies from intracellular combinatorial libraries reveals that cellular receptors are functionally pleiotropic.
Abstract The main purpose of this perspective is to build on the unexpected outcomes of previous laboratory experiments using antibody agonists to raise questions concerning how activation of a given receptor can be involved in inducing differentiation of cells along different pathways some of which may even derive from different lineages. While not yet answered, the question illustrates how the advent of agonists not present in nature may give a different dimension to the important problem of signal transduction. Thus, if one studies a natural agonist-receptor system one can learn details about its signal transdu...
Source: Current Opinion in Chemical Biology - January 23, 2015 Category: Biochemistry Authors: Yea K, Xie J, Zhang H, Zhang W, Lerner RA Tags: Curr Opin Chem Biol Source Type: research

PNA-encoded chemical libraries.
Abstract Peptide nucleic acid (PNA)-encoded chemical libraries along with DNA-encoded libraries have provided a powerful new paradigm for library synthesis and ligand discovery. PNA-encoding stands out for its compatibility with standard solid phase synthesis and the technology has been used to prepare libraries of peptides, heterocycles and glycoconjugates. Different screening formats have now been reported including selection-based and microarray-based methods that have yielded specific ligands against diverse target classes including membrane receptors, lectins and challenging targets such as Hsp70. PMID: ...
Source: Current Opinion in Chemical Biology - January 23, 2015 Category: Biochemistry Authors: Zambaldo C, Barluenga S, Winssinger N Tags: Curr Opin Chem Biol Source Type: research

Artificial hydrogenase: biomimetic approaches controlling active molecular catalysts.
This article reviews recent advances in the design and catalytic properties of artificial enzymes that mimic the hydrogenase active site and the outer coordination sphere in combination with a peptide or protein scaffold. PMID: 25617828 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - January 21, 2015 Category: Biochemistry Authors: Onoda A, Hayashi T Tags: Curr Opin Chem Biol Source Type: research

Metal-binding promiscuity in artificial metalloenzyme design.
Abstract This review presents recent examples of metal-binding promiscuity in protein scaffolds and highlights the effect of metal variation on catalytic functionality. Naturally evolved binding sites, as well as unnatural amino acids and cofactors can bind a diverse range of metals, including non-biological transition elements. Computational screening and rational design have been successfully used to create promiscuous binding-sites. Incorporation of non-native metals into proteins expands the catalytic range of transformations catalysed by enzymes and enhances their potential for application in chemicals synthe...
Source: Current Opinion in Chemical Biology - January 17, 2015 Category: Biochemistry Authors: Pordea A Tags: Curr Opin Chem Biol Source Type: research

Recent developments in enzyme promiscuity for carbon-carbon bond-forming reactions.
Abstract Numerous enzymes have been found to catalyze additional and completely different types of reactions relative to the natural activity they evolved for. This phenomenon, called catalytic promiscuity, has proven to be a fruitful guide for the development of novel biocatalysts for organic synthesis purposes. As such, enzymes have been identified with promiscuous catalytic activity for, one or more, eminent types of carbon-carbon bond-forming reactions like aldol couplings, Michael(-type) additions, Mannich reactions, Henry reactions, and Knoevenagel condensations. This review focuses on enzymes that promiscuo...
Source: Current Opinion in Chemical Biology - January 15, 2015 Category: Biochemistry Authors: Miao Y, Rahimi M, Geertsema EM, Poelarends GJ Tags: Curr Opin Chem Biol Source Type: research

Catalysts for RNA and DNA modification.
Abstract To study DNAs and RNAs it is often necessary to chemically modify them. Nature's strategy for nucleic acid modification is to use selective catalysts, and chemists have begun to emulate this conceptual approach. In this review we present a summary of catalytic approaches toward the construction of modified RNAs and DNAs and outline our opinions on where new research is needed. PMID: 25590584 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - January 12, 2015 Category: Biochemistry Authors: Gillingham D, Shahid R Tags: Curr Opin Chem Biol Source Type: research

Molecular recognition in protein modification with rhodium metallopeptides.
Abstract Chemical manipulation of natural, unengineered proteins is a daunting challenge which tests the limits of reaction design. By combining transition-metal or other catalysts with molecular recognition ideas, it is possible to achieve site-selective protein reactivity without the need for engineered recognition sequences or reactive sites. Some recent examples in this area have used ruthenium photocatalysis, pyridine organocatalysis, and rhodium(II) metallocarbene catalysis, indicating that the fundamental ideas provide opportunities for using diverse reactivity on complex protein substrates and in complex c...
Source: Current Opinion in Chemical Biology - January 9, 2015 Category: Biochemistry Authors: Ball ZT Tags: Curr Opin Chem Biol Source Type: research