Magnetic particle imaging for radiation-free, sensitive and high-contrast vascular imaging and cell tracking.
Abstract Magnetic particle imaging (MPI) is an emerging ionizing radiation-free biomedical tracer imaging technique that directly images the intense magnetization of superparamagnetic iron oxide nanoparticles (SPIOs). MPI offers ideal image contrast because MPI shows zero signal from background tissues. Moreover, there is zero attenuation of the signal with depth in tissue, allowing for imaging deep inside the body quantitatively at any location. Recent work has demonstrated the potential of MPI for robust, sensitive vascular imaging and cell tracking with high contrast and dose-limited sensitivity comparable to n...
Source: Current Opinion in Chemical Biology - May 10, 2018 Category: Biochemistry Authors: Zhou XY, Tay ZW, Chandrasekharan P, Yu EY, Hensley DW, Orendorff R, Jeffris KE, Mai D, Zheng B, Goodwill PW, Conolly SM Tags: Curr Opin Chem Biol Source Type: research

Synthetic genomics: a new venture to dissect genome fundamentals and engineer new functions.
Abstract Since the first synthetic gene was synthesized in 1970s, the efficiency and the capacity of made-to-order DNA sequence synthesis has increased by several orders of magnitude. Advances in DNA synthesis and assembly over the past years has resulted in a steep drop in price for custom made DNA. Similar effects were observed in DNA sequencing technologies which underpin DNA-reading projects. Today, synthetic DNA sequences with more than 10000bps and turn-around times of a few weeks are commercially available. This enables researchers to perform large-scale projects to write synthetic chromosomes and character...
Source: Current Opinion in Chemical Biology - May 8, 2018 Category: Biochemistry Authors: Schindler D, Dai J, Cai Y Tags: Curr Opin Chem Biol Source Type: research

Recent advances in DNA nanotechnology.
Abstract DNA is a powerful guiding molecule to achieve the precise construction of arbitrary structures and high-resolution organization of functional materials. The combination of sequence programmability, rigidity and highly specific molecular recognition in this molecule has resulted in a wide range of exquisitely designed DNA frameworks. To date, the impressive potential of DNA nanomaterials has been demonstrated from fundamental research to technological advancements in materials science and biomedicine. This review presents a summary of some of the most recent developments in structural DNA nanotechnology re...
Source: Current Opinion in Chemical Biology - May 8, 2018 Category: Biochemistry Authors: Chidchob P, Sleiman HF Tags: Curr Opin Chem Biol Source Type: research

Advances in gadolinium-based MRI contrast agent designs for monitoring biological processes in vivo.
Abstract The gadolinium-based contrast agents widely used in diagnostic MRI exams for 30 years are all small molecule agents that distribute into all extracellular spaces in tissues without providing any specific biological information. Although many 'responsive agent' designs have been presented over the past 20 years or so, none have found use in clinical diagnostic medicine at this point. This review summarizes some recent approaches taken to enhance the sensitivity of such gadolinium-based agents, to target them to specific tissue components, and to create new systems for monitoring specific biological process...
Source: Current Opinion in Chemical Biology - May 8, 2018 Category: Biochemistry Authors: Lux J, Sherry AD Tags: Curr Opin Chem Biol Source Type: research

Synthesis and semisynthesis of selenopeptides and selenoproteins.
Abstract The versatile chemistry of the genetically encoded amino acid selenocysteine (Sec) is employed in Nature to expand the reactivity of enzymes. In addition to, its role in biology, Sec is used in protein engineering to modify folding, stability, and reactivity of proteins, to introduce conjugations and to facilitate reactions. However, due to limitations related to Sec's insertion mechanism in Nature, much of the production of Sec containing peptides and proteins relies on synthesis and semisynthesis. Here, we review recent advances that have enabled the assembly of complicated selenoproteins, including nov...
Source: Current Opinion in Chemical Biology - April 30, 2018 Category: Biochemistry Authors: Liu J, Cheng R, Rozovsky S Tags: Curr Opin Chem Biol Source Type: research

Automated glycan assembly as an enabling technology.
Abstract Access to complex carbohydrates remains a limiting factor for the development of the glycosciences. Automated glycan assembly (AGA) has accelerated and simplified the synthetic process and, with the first commercially available instrument and building blocks, glycan synthesis can now be practiced by any chemist. All classes of glycans, including sulfated or sialylated carbohydrates and polysaccharides as long as 50mers are now accessible owing to optimized reaction conditions and new methodologies. These synthetic glycans have helped to understand many biological functions and to advance diagnostic and va...
Source: Current Opinion in Chemical Biology - April 28, 2018 Category: Biochemistry Authors: Pardo-Vargas A, Delbianco M, Seeberger PH Tags: Curr Opin Chem Biol Source Type: research

Organotrifluoroborates as prosthetic groups for Single-Step F18-Labeling of Complex Molecules.
Abstract To meet the long-standing challenge of a one-step, last-stage aqueous radiofluorination method for labeling large, water-soluble molecules such as peptides, we sought a mild aqueous fluorination reaction that uses organoboron compositions, which are readily fluorinated in mild aqueous acid to give 18F-labeled organotrifluoroborates. This robust reaction now provides new 18F-labeled radioprosthetic groups that can be pre-conjugated to peptides and other polar molecules, and then labeled with aqueous no-carrier-added (NCA) [18F]fluoride ion in a single step. A key application facilitated by this method is t...
Source: Current Opinion in Chemical Biology - April 20, 2018 Category: Biochemistry Authors: Perrin DM Tags: Curr Opin Chem Biol Source Type: research

Peptide modification and cyclization via transition-metal catalysis.
Abstract Transition-metal catalysis has unlocked new paradigms for the late-stage modification and cyclization of peptides by harnessing the innate reactivity of proteinogenic amino acids. The field is rapidly evolving, with recent advances encompassing three fundamental areas-heteroatom couplings, decarboxylative cross-couplings, and C-H functionalizations-which have markedly extended the scope of conventional peptide modification and bioconjugation strategies. The advances outlined herein facilitate access to high-value peptide targets with promising applications in materials science and drug discovery. PMI...
Source: Current Opinion in Chemical Biology - April 12, 2018 Category: Biochemistry Authors: Malins LR Tags: Curr Opin Chem Biol Source Type: research

Acyl donors for native chemical ligation.
This article reviews the recent advances in the design of C-terminal acyl donors, their precursors and surrogates, and highlights some noteworthy progress that may lead the future direction of protein chemical synthesis. PMID: 29654943 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - April 11, 2018 Category: Biochemistry Authors: Yan B, Shi W, Ye L, Liu L Tags: Curr Opin Chem Biol Source Type: research

Leading approaches in synthetic epigenetics for novel therapeutic strategies.
Abstract In recent years, our knowledge of the epigenetic functions regulated by post-translational modifications (PTMs) of histones, and their role in various diseases, has expanded rapidly, opening the way to novel therapeutic strategies that treat epigenetic abnormalities. Many of the current approaches have been focusing on the chemical inhibition of histone-modifying enzymes to modulate histone PTM states for attaining therapeutic effects. However, recent developments in chemistry and molecular biology have contributed to the emergence of new methods that introduce histone PTMs entirely through artificial mea...
Source: Current Opinion in Chemical Biology - April 6, 2018 Category: Biochemistry Authors: Yamatsugu K, Kawashima SA, Kanai M Tags: Curr Opin Chem Biol Source Type: research

Recent progress in photoacoustic molecular imaging.
Abstract By acoustically detecting the optical absorption contrast, photoacoustic (PA) tomography (PAT) has broken the penetration limits of traditional high-resolution optical imaging. Through spectroscopic analysis of the target's optical absorption, PAT can identify a wealth of endogenous and exogenous molecules and thus is inherently capable of molecular imaging with high sensitivity. PAT's molecular sensitivity is uniquely accompanied by non-ionizing radiation, high spatial resolution, and deep penetration in biological tissues, which other optical imaging modalities cannot achieve yet. In this concise review...
Source: Current Opinion in Chemical Biology - April 6, 2018 Category: Biochemistry Authors: Yao J, Wang LV Tags: Curr Opin Chem Biol Source Type: research

Molecular imaging agents for ultrasound.
Abstract Ultrasound (US) imaging is a safe, sensitive and affordable imaging modality with a wide usage in the clinic. US signal can be further enhanced by using echogenic contrast agents (UCAs) which amplify the US signal. Developments in UCAs which are targeted to sites of disease allow the use of US imaging to provide molecular information. Unfortunately, traditional UCAs are too large to leave the vascular space limiting the application of molecular US to intravascular markers. In this mini review, we highlight the most recent reports on the application of molecular US imaging in the clinic and summarize the l...
Source: Current Opinion in Chemical Biology - April 6, 2018 Category: Biochemistry Authors: Zlitni A, Gambhir SS Tags: Curr Opin Chem Biol Source Type: research

Emergence of two near-infrared windows for in vivo and intraoperative SERS.
Abstract Two clear windows in the near-infrared (NIR) spectrum are of considerable current interest for in vivo molecular imaging and spectroscopic detection. The main rationale is that near-infrared light can penetrate biological tissues such as skin and blood more efficiently than visible light because these tissues scatter and absorb less light at longer wavelengths. The first clear window, defined as light wavelengths between 650nm and 950nm, has been shown to be far superior for in vivo and intraoperative optical imaging than visible light. The second clear window, operating in the wavelength range of 1000-17...
Source: Current Opinion in Chemical Biology - April 6, 2018 Category: Biochemistry Authors: Lane LA, Xue R, Nie S Tags: Curr Opin Chem Biol Source Type: research

Synthetic fermentation of bioactive molecules.
Abstract The concept of synthetic fermentation is to 'grow' complex organic molecules in a controlled and predictable manner by combining small molecule building blocks in water-without the need for reagents, enzymes, or organisms. This approach mimics the production of small mixtures of structurally related natural products by living organisms, particularly microbes, under conditions compatible with direct screening of the cultures for biological activity. This review discusses the development and implementation of this concept, its use for the discovery of protease inhibitors, its basis as a chemistry outreach p...
Source: Current Opinion in Chemical Biology - April 5, 2018 Category: Biochemistry Authors: Stepek IA, Bode JW Tags: Curr Opin Chem Biol Source Type: research

Racemic & quasi-racemic protein crystallography enabled by chemical protein synthesis.
Racemic & quasi-racemic protein crystallography enabled by chemical protein synthesis. Curr Opin Chem Biol. 2018 Apr 04;46:1-9 Authors: Kent SB Abstract A racemic protein mixture can be used to form centrosymmetric crystals for structure determination by X-ray diffraction. Both the unnatural d-protein and the corresponding natural l-protein are made by total chemical synthesis based on native chemical ligation-chemoselective condensation of unprotected synthetic peptide segments. Racemic protein crystallography is important for structure determination of the many natural protein molecules that are...
Source: Current Opinion in Chemical Biology - April 4, 2018 Category: Biochemistry Authors: Kent SB Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Biocatalysis and biotransformation: The golden age of biocatalysis.
PMID: 29526305 [PubMed - in process] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - March 13, 2018 Category: Biochemistry Authors: Turner NJ, Kumar R Tags: Curr Opin Chem Biol Source Type: research

Editorial overview: Bioinorganic chemistry: Bio-medicinal functions of metal complexes.
PMID: 29526306 [PubMed - in process] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - March 13, 2018 Category: Biochemistry Authors: Guo Z, Zhao J Tags: Curr Opin Chem Biol Source Type: research

DNA methylation as a genomic marker of exposure to chemical and environmental agents.
Abstract Recent progress in interpreting comprehensive genetic and epigenetic profiles for human cellular states has contributed new insights into the developmental origins of disease, elucidated novel signalling pathways and enhanced drug discovery programs. A similar comprehensive approach to decoding the epigenetic readouts from chemical challenges in vivo would yield new paradigms for monitoring and assessing environmental exposure in model systems and humans. PMID: 29505975 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - March 2, 2018 Category: Biochemistry Authors: Meehan RR, Thomson JP, Lentini A, Nestor CE, Pennings S Tags: Curr Opin Chem Biol Source Type: research

Synthetic post-translational modification of histones.
Abstract Chromatin is the physiological template of genetic information in all eukaryotic cells, a highly organised complex of DNA and histone proteins central in regulating gene expression and genome organisation. A multitude of histone post-translational modifications (PTMs) have been discovered, providing a glance into the complex interplay of these epigenetic marks in cellular processes. In the last decade, synthetic and chemical biology techniques have emerged to study these modifications, including genetic code expansion, histone semisynthesis and post-translational chemical mutagenesis. These methods allow ...
Source: Current Opinion in Chemical Biology - February 28, 2018 Category: Biochemistry Authors: Nadal S, Raj R, Mohammed S, Davis BG Tags: Curr Opin Chem Biol Source Type: research

Studies of biochemical crosstalk in chromatin with semisynthetic histones.
Abstract Reversible post-translational modifications of histone proteins in eukaryotic chromatin are closely tied to gene function and cellular development. Specific combinations of histone modifications, or marks, are implicated in distinct DNA-templated processes mediated by a range of chromatin-associated enzymes that install, erase and interpret the histone code. Mechanistic studies of the precise biochemical relationship between sets of marks and their effects on chromatin function are significantly complicated by the dynamic nature and heterogeneity of marks in cellular chromatin. Protein semisynthesis is a ...
Source: Current Opinion in Chemical Biology - February 26, 2018 Category: Biochemistry Authors: Leonen CJA, Upadhyay E, Chatterjee C Tags: Curr Opin Chem Biol Source Type: research

Chemical chromatin ubiquitylation.
Abstract Histone modifications dynamically regulate chromatin structure and function, thereby mediating many processes that require access to DNA. Chemical protein synthesis has emerged as a powerful approach for generating homogeneously modified histone analogues in workable amounts for subsequent incorporation into nucleosome arrays for biochemical, functional and structural studies. This short review focuses on the strength of total chemical protein synthesis and semisynthetic approaches to generate ubiquitylated histones in their native or non-native forms and the utility of these analogues to decode the role ...
Source: Current Opinion in Chemical Biology - February 16, 2018 Category: Biochemistry Authors: Jbara M, Sun H, Kamnesky G, Brik A Tags: Curr Opin Chem Biol Source Type: research

Letter to the Editor.
cute; PMID: 29452735 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - February 13, 2018 Category: Biochemistry Authors: Furka Á Tags: Curr Opin Chem Biol Source Type: research

Reply to Letter to the Editor.
PMID: 29452736 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - February 13, 2018 Category: Biochemistry Authors: Lam KS Tags: Curr Opin Chem Biol Source Type: research

Epigenetic chromatin modification by amber suppression technology.
Abstract The genetic incorporation of unnatural amino acids (UAAs) into proteins by amber suppression technology provides unique avenues to study protein structure, function and interactions both in vitro and in living cells and organisms. This approach has been particularly useful for studying mechanisms of epigenetic chromatin regulation, since these extensively involve dynamic changes in structure, complex formation and posttranslational modifications that are difficult to access by traditional approaches. Here, we review recent achievements in this field, emphasizing UAAs that help to unravel protein-protein i...
Source: Current Opinion in Chemical Biology - February 13, 2018 Category: Biochemistry Authors: Neumann H, Neumann-Staubitz P, Witte A, Summerer D Tags: Curr Opin Chem Biol Source Type: research

Harnessing natural DNA modifying activities for editing of the genome and epigenome.
Abstract The introduction of site-specific DNA modifications to the genome or epigenome presents great opportunities for manipulating biological systems. Such changes are now possible through the combination of DNA-modifying enzymes with targeting modules, including dCas9, that can localize the enzymes to specific sites. In this review, we take a DNA modifying enzyme-centric view of recent advances. We highlight the variety of natural DNA-modifying enzymes-including DNA methyltransferases, oxygenases, deaminases, and glycosylases-that can be used for targeted editing and discuss how insights into the structure and...
Source: Current Opinion in Chemical Biology - February 13, 2018 Category: Biochemistry Authors: DeNizio JE, Schutsky EK, Berrios KN, Liu MY, Kohli RM Tags: Curr Opin Chem Biol Source Type: research

Unique insights to intrinsically disordered proteins provided by ion mobility mass spectrometry.
Abstract Entire functional proteins as well as large regions of proteins lack structural elements which are resolvable via crystallography or NMR. These intrinsically disordered proteins (IDPs) or regions (IDRs) are often involved in cell regulation processes, for example in signalling hubs and as a result aberrant behaviour can cause or be representative of disease. As a consequence there is a pressing need to develop alternative structural methods for IDPs and the interactions that they may form with other proteins and/or with potential inhibitors of binding. One such method is ion mobility mass spectrometry (IM...
Source: Current Opinion in Chemical Biology - February 8, 2018 Category: Biochemistry Authors: Stuchfield D, Barran P Tags: Curr Opin Chem Biol Source Type: research

Enzymatic amidation for industrial applications.
Abstract Nature has developed a robust toolbox for the formation of amide bonds, enabling a variety of disconnections applicable to small molecule synthesis. In spite of this, the exploitation of biocatalytic techniques for industrial synthesis remains limited to a few very important cases. This review discusses previously demonstrated techniques for the biocatalytic synthesis of amide bonds, reviews examples of industrial scale-up of these techniques, and identifies a number of limitations to the scalability within the current state of the art. PMID: 29414531 [PubMed - as supplied by publisher] (Source: Curr...
Source: Current Opinion in Chemical Biology - February 3, 2018 Category: Biochemistry Authors: Dorr BM, Fuerst DE Tags: Curr Opin Chem Biol Source Type: research

Halogenases: powerful tools for biocatalysis (mechanisms applications and scope).
PMID: 29414530 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology)
Source: Current Opinion in Chemical Biology - February 1, 2018 Category: Biochemistry Authors: Gkotsi DS, Dhaliwal J, McLachlan MM, Mulholand KR, Goss RJ Tags: Curr Opin Chem Biol Source Type: research

Understanding protein-drug interactions using ion mobility-mass spectrometry.
Abstract Ion mobility-mass spectrometry (IM-MS) is an important addition to the analytical toolbox for the structural evaluation of proteins, and is enhancing many areas of biophysical analysis. Disease-associated proteins, including enzymes such as protein kinases, transcription factors exemplified by p53, and intrinsically disordered proteins, including those prone to aggregation, are all amenable to structural analysis by IM-MS. In this review we discuss how this powerful technique can be used to understand protein conformational dynamics and aggregation pathways, and in particular, the effect that small molecu...
Source: Current Opinion in Chemical Biology - January 10, 2018 Category: Biochemistry Authors: Eyers CE, Vonderach M, Ferries S, Jeacock K, Eyers PA Tags: Curr Opin Chem Biol Source Type: research

Ion mobility in the pharmaceutical industry: an established biophysical technique or still niche?
Abstract Over the past decade ion mobility (IM) coupled with mass spectrometry (MS) has emerged as a wide spread analytical technique, utilized in research areas ranging from small molecule to proteins analyzed under native-MS and solution conditions. The ion-neutral collision cross section (Ω) derived from an IM experiment can be used to make inferences about the ion's size, shape and charge distribution, when compared to molecular dynamic (MD) or quantum mechanically (QM) derived candidate structures. IM can also be used as an orthogonal separation technique when coupled with liquid chromatographic (LC) se...
Source: Current Opinion in Chemical Biology - January 4, 2018 Category: Biochemistry Authors: Campuzano ID, Lippens JL Tags: Curr Opin Chem Biol Source Type: research

Activity-based sensing fluorescent probes for iron in biological systems.
Abstract Iron is an essential nutrient for life, and its capacity to cycle between different oxidation states is required for processes spanning oxygen transport and respiration to nucleotide synthesis and epigenetic regulation. However, this same redox ability also makes iron, if not regulated properly, a potentially dangerous toxin that can trigger oxidative stress and damage. New methods that enable monitoring of iron in living biological systems, particularly in labile Fe2+ forms, can help identify its contributions to physiology, aging, and disease. In this review, we summarize recent developments in activity...
Source: Current Opinion in Chemical Biology - January 4, 2018 Category: Biochemistry Authors: Aron AT, Reeves AG, Chang CJ Tags: Curr Opin Chem Biol Source Type: research

Mass spectrometry beyond the native state.
Abstract Native mass spectrometry allows the study of proteins by probing in vacuum the interactions they form in solution. It is a uniquely useful approach for structural biology and biophysics due to the high resolution of separation it affords, allowing the concomitant interrogation of multiple protein components with high mass accuracy. At its most basic, native mass spectrometry reports the mass of intact proteins and the assemblies they form in solution. However, the opportunities for more detailed characterisation are extensive, enabled by the exquisite control of ion motion that is possible in vacuum. Here...
Source: Current Opinion in Chemical Biology - December 27, 2017 Category: Biochemistry Authors: Chandler SA, Benesch JL Tags: Curr Opin Chem Biol Source Type: research

Improving the discovery of secondary metabolite natural products using ion mobility-mass spectrometry.
Abstract Secondary metabolite discovery requires an unbiased, comprehensive workflow to detect unknown unknowns for which little to no molecular knowledge exists. Untargeted mass spectrometry-based metabolomics is a powerful platform, particularly when coupled with ion mobility for high-throughput gas-phase separations to increase peak capacity and obtain gas-phase structural information. Ion mobility data are described by the amount of time an ion spends in the drift cell, which is directly related to an ion's collision cross section (CCS). The CCS parameter describes the size, shape, and charge of a molecule and...
Source: Current Opinion in Chemical Biology - December 26, 2017 Category: Biochemistry Authors: Schrimpe-Rutledge AC, Sherrod SD, McLean JA Tags: Curr Opin Chem Biol Source Type: research

Transaminases for chiral amine synthesis.
Abstract Amine transaminases are important biocatalysts for the synthesis of chiral primary amines. Unlike many enzymes that have been employed for the synthesis of optically active amines, amine transaminases are capable of asymmetric synthesis and do not rely on costly cofactors that must be regenerated in situ. However, their application as general catalysts for the preparation of amines is hampered by a limited substrate scope, substrate and (co)product inhibition and difficulties associated with displacing challenging reaction equilibrium. There has been important progress made to overcome these challenges, i...
Source: Current Opinion in Chemical Biology - December 23, 2017 Category: Biochemistry Authors: Gomm A, O'Reilly E Tags: Curr Opin Chem Biol Source Type: research

Advances in mass spectrometry imaging coupled to ion mobility spectrometry for enhanced imaging of biological tissues.
Abstract Tissues present complex biochemical and morphological composition associated with their various cell types and physiological functions. Mass spectrometry (MS) imaging technologies are powerful tools to investigate the molecular information from biological tissue samples and visualize their complex spatial distributions. Coupling of gas-phase ion mobility spectrometry (IMS) technologies to MS imaging has been increasingly explored to improve performance for biological tissue imaging. This approach allows improved detection of low abundance ions and separation of isobaric molecular species, thus resulting i...
Source: Current Opinion in Chemical Biology - December 21, 2017 Category: Biochemistry Authors: Sans M, Feider CL, Eberlin LS Tags: Curr Opin Chem Biol Source Type: research

Genetically encoded fluorescent sensors for measuring transition and heavy metals in biological systems.
Abstract Great progress has been made in expanding the repertoire of genetically encoded fluorescent sensors for monitoring intracellular transition metals (TMs). This powerful toolkit permits dynamic and non-invasive detection of TMs with high spatial-temporal resolution, which enables us to better understand the roles of TM homeostasis in both physiological and pathological settings. Here we summarize the recent development of genetically encoded fluorescent sensors for intracellular detection of TMs such as zinc and copper, as well as heavy metals including lead, cadmium, mercury, and arsenic. PMID: 292752...
Source: Current Opinion in Chemical Biology - December 21, 2017 Category: Biochemistry Authors: Hao Z, Zhu R, Chen PR Tags: Curr Opin Chem Biol Source Type: research

Biocatalytic reduction of activated CC-bonds and beyond: emerging trends.
Abstract The biocatalytic reduction of activated CC-bonds is dominated by ene-reductases from the Old Yellow Enzyme family, which gained broad practical use owing to exquisite stereoselectivity combined with wide substrate scope. Protein diversity is fostered by mining distinct protein classes and by implementing protein engineering techniques. Recent efforts are focusing on expanding the chemical complexity of the product portfolio, either through substrate functionalization or design of multi-step reactions. This review also highlights unusual chemistries catalyzed by ene-reductases and presents emerging methodo...
Source: Current Opinion in Chemical Biology - December 21, 2017 Category: Biochemistry Authors: Winkler CK, Faber K, Hall M Tags: Curr Opin Chem Biol Source Type: research

Recent advances in enzymatic oxidation of alcohols.
Abstract Enzymatic alcohol oxidation plays an important role in chemical synthesis. In the past two years, new alcohol oxidation enzymes were developed through genome-mining and protein engineering, such as new copper radical oxidases with broad substrate scope, alcohol dehydrogenases with altered cofactor preference and a flavin-dependent alcohol oxidase with enhanced oxygen coupling. New cofactor recycling methods were reported for alcohol dehydrogenase-catalyzed oxidation with photocatalyst and coupled glutaredoxin-glutathione reductase as promising examples. Different alcohol oxidation systems were used for th...
Source: Current Opinion in Chemical Biology - December 16, 2017 Category: Biochemistry Authors: Liu J, Wu S, Li Z Tags: Curr Opin Chem Biol Source Type: research

Contemporary glycomic approaches using ion mobility-mass spectrometry.
Abstract Characterization of complex oligosaccharides has historically required extensive sample handling and separations before analysis using nuclear magnetic resonance spectroscopy and electron impact mass spectra following hydrolysis, derivatization, and gas chromatographic separation. Advances in liquid chromatography separations and tandem mass spectrometry have expanded the range of intact glycan analysis, but carbohydrate structure and conformation-integral chemical characteristics-are often difficult to assess with minimal amounts of sample in a rapid fashion. Because ion mobility spectrometry (IMS) separ...
Source: Current Opinion in Chemical Biology - December 14, 2017 Category: Biochemistry Authors: Morrison KA, Clowers BH Tags: Curr Opin Chem Biol Source Type: research

Functionalization of protein crystals with metal ions, complexes and nanoparticles.
Abstract Self-assembled proteins have specific functions in biology. With inspiration provided by natural protein systems, several artificial protein assemblies have been constructed via site-specific mutations or metal coordination, which have important applications in catalysis, material and bio-supramolecular chemistry. Similar to natural protein assemblies, protein crystals have been recognized as protein assemblies formed of densely-packed monomeric proteins. Protein crystals can be functionalized with metal ions, metal complexes or nanoparticles via soaking, co-crystallization, creating new metal binding sit...
Source: Current Opinion in Chemical Biology - December 12, 2017 Category: Biochemistry Authors: Abe S, Maity B, Ueno T Tags: Curr Opin Chem Biol Source Type: research

Magnifying ion mobility spectrometry-mass spectrometry measurements for biomolecular structure studies.
Abstract Ion mobility spectrometry-mass spectrometry (IMS-MS) provides information about the structures of gas-phase ions in the form of a collision cross section (CCS) with a neutral buffer gas. Indicating relative ion size, a CCS value alone is of limited utility. Although such information can be used to propose different conformer types, finer details of structure are not captured. The increased accessibility of IMS-MS measurements with commercial instrumentation in recent years has ballooned its usage in combination with separate measurements to provide enhanced data from which greater structural inferences ca...
Source: Current Opinion in Chemical Biology - December 11, 2017 Category: Biochemistry Authors: Majuta SN, Maleki H, Kiani Karanji A, Attanyake K, Loch E, Valentine SJ Tags: Curr Opin Chem Biol Source Type: research

Single molecule force spectroscopy: a new tool for bioinorganic chemistry.
Abstract Metalloproteins are essential in biology. The incorporation of metal ion into metalloproteins significantly expands protein functionality and enhances protein stability. Over the last few years, atomic force microscopy-based single molecule force spectroscopy (SMFS) has evolved into a unique tool allowing for probing metalloproteins and metalligand bonds one molecule/bond at a time. Mechanical strength of a wide variety of metalligand bonds has been measured in metal-ligand complexes as well as in metalloproteins, providing detailed information of their underlying free energy profiles and the influence of...
Source: Current Opinion in Chemical Biology - December 6, 2017 Category: Biochemistry Authors: Li H, Zheng P Tags: Curr Opin Chem Biol Source Type: research

Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches.
Abstract Lipids are a vital class of molecules that play important and varied roles in biological processes, however, fully understanding these roles is extremely difficult due to the immense number and diversity of possible lipid species. While recent advances in chromatography and high resolution mass spectrometry have greatly progressed knowledge about distinct lipid species and functions, effectively separating many lipids still remains problematic. Isomeric lipids have made lipid characterization especially difficult and occur due to subclasses having the same chemical composition, or species having multiple ...
Source: Current Opinion in Chemical Biology - December 6, 2017 Category: Biochemistry Authors: Zheng X, Smith RD, Baker ES Tags: Curr Opin Chem Biol Source Type: research

Collision induced unfolding of isolated proteins in the gas phase: past, present, and future.
Abstract Rapidly characterizing the three-dimensional structures of proteins and the multimeric machines they form remains one of the great challenges facing modern biological and medical sciences. Ion mobility-mass spectrometry based techniques are playing an expanding role in characterizing these functional complexes, especially in drug discovery and development workflows. Despite this expansion, ion mobility-mass spectrometry faces many challenges, especially in the context of detecting small differences in protein tertiary structure that bear functional consequences. Collision induced unfolding is an ion mobil...
Source: Current Opinion in Chemical Biology - December 2, 2017 Category: Biochemistry Authors: Dixit SM, Polasky DA, Ruotolo BT Tags: Curr Opin Chem Biol Source Type: research

Bridging the structural gap of glycoproteomics with ion mobility spectrometry.
Abstract Over the past two decades mass spectrometry (MS) has enabled high throughput studies on the level of a complex proteome. While it has similarly advanced glycobiology, the level of progress has been more restrained. This is in large part due to the diversity and complexity of carbohydrate structures. While MS is now routinely used for glycobiology, it suffers from a critical limitation, that is the inability to resolve isobaric structures. Since so many structurally and functionally distinct carbohydrates are indistinguishable by MS, additional techniques are needed for detailed structural analysis. Ion mo...
Source: Current Opinion in Chemical Biology - December 1, 2017 Category: Biochemistry Authors: Mookherjee A, Guttman M Tags: Curr Opin Chem Biol Source Type: research

Methane to bioproducts: the future of the bioeconomy?
Abstract Methanotrophs have been studied since the 1970s, but interest has increased tremendously in recent years due to their potential to transform methane into valuable bioproducts. The vast quantity of available methane and the low price of methane as natural gas have helped to spur this interest. The most well-studied, biologically-derived products from methane include methanol, polyhydroxyalkanoates, and single cell protein. However, many other high-interest chemicals such as biofuels or high-value products such as ectoine could be made industrially relevant through metabolic engineering. Although challenges...
Source: Current Opinion in Chemical Biology - November 29, 2017 Category: Biochemistry Authors: Pieja AJ, Morse MC, Cal AJ Tags: Curr Opin Chem Biol Source Type: research

Mitochondrial dynamics tracking with iridium(III) complexes.
Abstract Since the discovery of mitochondrial dynamics, demand for dyes able to track this process has been a great. In contrast to static imaging, dynamic tracking requires superior photostability, low cytotoxicity and high resistance to the loss of mitochondrial membrane potential as well as appreciable tolerance to environmental changes. Recently, a variety of phosphorescent Ir(III) complexes have been found to localize in mitochondria and their applications as mitochondrial dynamics trackers have been assessed in cell monolayers, 3D MCSs and live animals. The examples presented here demonstrate that Ir(III) co...
Source: Current Opinion in Chemical Biology - November 22, 2017 Category: Biochemistry Authors: Chen Y, Rees TW, Ji L, Chao H Tags: Curr Opin Chem Biol Source Type: research

Protein lipoylation: an evolutionarily conserved metabolic regulator of health and disease.
Abstract Lipoylation is a rare, but highly conserved lysine posttranslational modification. To date, it is known to occur on only four multimeric metabolic enzymes in mammals, yet these proteins are staples in the core metabolic landscape. The dysregulation of these mitochondrial proteins is linked to a range of human metabolic disorders. Perhaps most striking is that lipoylation itself, the proteins that add or remove the modification, as well as the proteins it decorates are all evolutionarily conserved from bacteria to humans, highlighting the importance of this essential cofactor. Here, we discuss the biologic...
Source: Current Opinion in Chemical Biology - November 20, 2017 Category: Biochemistry Authors: Rowland EA, Snowden CK, Cristea IM Tags: Curr Opin Chem Biol Source Type: research

The application of ion mobility mass spectrometry to metabolomics.
Abstract Mass spectrometry-based metabolomics is being increasingly utilized in various research fields including investigating human diseases, nutrition, industrial applications, and plant/natural products studies. Although new analytical approaches have enhanced the performance of metabolomic analyses, significant challenges associated with throughput, metabolome coverage, and compound identification still exist. Ion mobility mass spectrometry offers great potential for improving throughput and depth of coverage in metabolomics experiments. For example, multi-dimensional, structural resolution offered by ion mob...
Source: Current Opinion in Chemical Biology - November 18, 2017 Category: Biochemistry Authors: Zhang X, Quinn K, Cruickshank-Quinn C, Reisdorph R, Reisdorph N Tags: Curr Opin Chem Biol Source Type: research

Ambient surface mass spectrometry-ion mobility spectrometry of intact proteins.
Abstract Ambient surface mass spectrometry encompasses a broad range of sampling and ionization techniques. To date, only a small subset of these, based on liquid microjunction extraction, have proven suitable for intact protein analysis from thin tissue sections. Liquid extraction surface analysis shows particular promise for this application. Recently, a range of ion mobility spectrometry approaches have been coupled with ambient mass spectrometry. Improvements in signal-to-noise ratios, decreased chemical noise and separation of molecular classes have been described for the analysis of various biological substr...
Source: Current Opinion in Chemical Biology - November 18, 2017 Category: Biochemistry Authors: Griffiths RL, Kocurek KI, Cooper HJ Tags: Curr Opin Chem Biol Source Type: research