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Elsevier

Publications in this journal

• Iron sulfur cluster proteins and microbial regulation: implications for understanding tuberculosis

  Authors: Saini V, Farhana A, Glasgow JN, Steyn AJ

  Current Opinion in Chemical Biology.

• Iron sulfur cluster proteins and microbial regulation: implications for understanding tuberculosis

  Authors: Vikram Saini, Aisha Farhana, Joel Glasgow, Adrie JC Steyn

  Current Opinion in Chemical Biology.

• A repulsive field: advances in the electrostatics of the ion atmosphere.

  Authors: Vincent B Chu, Yu Bai, Jan Lipfert, Daniel Herschlag, Sebastian Doniach

  Current opinion in chemical biology.

  The large electrostatic repulsion arising from the negatively charged backbone of RNA molecules presents a large barrier to folding. Solution counterions assist in the folding process by screeningThe large electrostatic repulsion arising from the negatively charged backbone of RNA molecules presents a large barrier to folding. Solution counterions assist in the folding process by screening this electrostatic repulsion. While early research interpreted the effect of these counterions in terms of an empirical ligand-binding model, theories based on physical models have supplanted them and revised our view of the roles that ions play in folding. Instead of specific ion-binding sites, most ions in solution interact inside an 'ion atmosphere'-a fluctuating cloud of nonspecifically associated ions surrounding any charged molecule. Recent advances in experiments have begun the task of characterizing the ion atmosphere, yielding valuable data that have revealed deficiencies in Poisson-Boltzmann theory, the most widely used theory of the ion atmosphere. The continued development of experiments will help guide the development of improved theories, with the ultimate goal of understanding RNA folding and function and nucleic acid/protein interactions from a quantitative perspective.

• Expanding the scope of chemoselective peptide ligations in chemical biology.

  Authors: Anouk Dirksen, Philip E Dawson

  Current opinion in chemical biology.

  Chemoselective ligation methods have increased the efficiency of bioconjugation, enabling complex macromolecules to be assembled. In particular, these methods have been utilized for the ligation andChemoselective ligation methods have increased the efficiency of bioconjugation, enabling complex macromolecules to be assembled. In particular, these methods have been utilized for the ligation and modification of peptides and proteins. The chemical synthesis of proteins from unprotected peptide fragments has enabled the introduction of unnatural amino acids, site-specific isotopic labeling, and the site-specific attachment of affinity tags or labels for imaging. A greater insight into current ligation methods has led to higher reaction rates, higher reaction yields, and greater biocompatibility, thereby increasing the impact of chemoselective ligation reactions in chemical biology.

• Peptides and peptidomimetics as prototypes.

  Authors: Helma Wennemers, Ronald T Raines

  Current opinion in chemical biology.

• Editorial overview: exploring the vast dynamic range of RNA dynamics.

  Authors: Philip C Bevilacqua, Rick Russell

  Current opinion in chemical biology.

• Exploring RNA folding one molecule at a time.

  Authors: Elvin A Alemán, Rajan Lamichhane, David Rueda

  Current opinion in chemical biology.

  RNA molecules fold into stable native structures to perform their biological function. RNA folding can be influenced by ions, co-factors, and proteins through numerous mechanisms. Understanding theseRNA molecules fold into stable native structures to perform their biological function. RNA folding can be influenced by ions, co-factors, and proteins through numerous mechanisms. Understanding these mechanisms at the molecular level is important for elucidating the structure-function relationship in biologically important RNAs. Recent developments in single molecule spectroscopy have provided new approaches to investigate RNA folding and have allowed identification of kinetic intermediates that would otherwise remain hidden in ensemble-averaged experiments. Here we summarize some of these developments, which provide new insight into the effect of Mg(2+) ions in RNA folding landscapes, the role of cooperativity in RNA tertiary folding, the stepwise folding of RNA during transcription, and the hierarchical assembly of RNA-protein complexes.

• Structural dynamics of the ribosome.

  Authors: Andrei Korostelev, Dmitri N Ermolenko, Harry F Noller

  Current opinion in chemical biology.

  Protein synthesis is inherently a dynamic process, requiring both small-scale and large-scale movements of tRNA and mRNA. It has long been suspected that these movements might be coupled toProtein synthesis is inherently a dynamic process, requiring both small-scale and large-scale movements of tRNA and mRNA. It has long been suspected that these movements might be coupled to conformational changes in the ribosome, and in its RNA moieties in particular. Recently, the nature of ribosome structural dynamics has begun to emerge from a combination of approaches, most notably cryo-EM, X-ray crystallography, and FRET. Ribosome movement occurs both on a grand scale, as in the intersubunit rotational movements that are coupled to tRNA-mRNA translocation, and in intricate localized rearrangements such as those that accompany codon-anticodon recognition and peptide bond formation. In spite of much progress, our understanding of the mechanics of translation is now beset with countless new questions, reflecting the vast molecular architecture of the ribosome itself.

• Experimental analyses of the chemical dynamics of ribozyme catalysis.

  Authors: Michael E Harris, Adam G Cassano

  Current opinion in chemical biology.

  Most ribozymes in Nature catalyze alcoholysis or hydrolysis of RNA phosphodiester bonds. Studies of the corresponding non-enzymatic reactions reveal a complex mechanistic landscape allowing for aMost ribozymes in Nature catalyze alcoholysis or hydrolysis of RNA phosphodiester bonds. Studies of the corresponding non-enzymatic reactions reveal a complex mechanistic landscape allowing for a variety of transition states and both concerted and stepwise mechanisms. High-resolution structures, incisive biochemical studies and computer simulations are providing glimpses into how ribozyme catalyzed reactions traverse this landscape. However, direct experimental tests of such mechanistic detail at the chemical level are not easily achieved. Kinetic isotope effects (KIEs) probe directly the differences in the vibrational 'environment' of the atoms undergoing chemical transformation on going from the ground state to the transition state. Thus, KIEs can in principle provide direct information about transition state bonding and so may be instrumental in evaluating possible transition states for ribozyme catalyzed reactions. Understanding charge distribution in the transitions state may help resolve how rate acceleration is accomplished and perhaps the similarities and differences in how RNA and protein active sites operate. Several barriers to successful application of KIE analysis to ribozymes have recently been overcome, and new chemical details are beginning to emerge.

• RNA in motion.

  Authors: Kathleen B Hall

  Current opinion in chemical biology.

  Although RNA duplex regions are highly structured and inflexible, other elements of an RNA molecule are capable of dynamic motions. These flexible regions are the sites of interactions with smallAlthough RNA duplex regions are highly structured and inflexible, other elements of an RNA molecule are capable of dynamic motions. These flexible regions are the sites of interactions with small molecules, proteins, and other RNAs, yet there are few descriptions of these regions that include the timescale and amplitude of their motions. No one technique is sufficient to accurately describe these motions, but the combination of in vitro methods, particularly NMR relaxation methods, and more robust in silico methods, is beginning to yield the type of data that can be used to understand RNA function. Very few RNAs have been described by both techniques, and here one such RNA and one RNA:protein complex are reviewed.

• Olefin metathesis for chemical biology.

  Authors: Joseph B Binder, Ronald T Raines

  Current opinion in chemical biology.

  Chemical biology relies on effective synthetic chemistry for building molecules to probe and modulate biological function. Olefin metathesis in organic solvents is a valuable addition to thisChemical biology relies on effective synthetic chemistry for building molecules to probe and modulate biological function. Olefin metathesis in organic solvents is a valuable addition to this armamentarium, and developments during the previous decade are enabling metathesis in aqueous solvents for the manipulation of biomolecules. Functional group-tolerant ruthenium metathesis catalysts modified with charged moieties or hydrophilic polymers are soluble and active in water, enabling ring-opening metathesis polymerization, cross metathesis, and ring-closing metathesis. Alternatively, conventional hydrophobic ruthenium complexes catalyze a similar array of metathesis reactions in mixtures of water and organic solvents. This strategy has enabled cross metathesis on the surface of a protein. Continuing developments in catalyst design and methodology will popularize the bioorthogonal reactivity of metathesis.

• Peptides as protein-binding site mimetics.

  Authors: Jutta Eichler

  Current opinion in chemical biology.

  The rational/structure-based design and/or combinatorial development of molecules capable of structurally and functionally mimicking the binding sites of proteins represents a promising strategy forThe rational/structure-based design and/or combinatorial development of molecules capable of structurally and functionally mimicking the binding sites of proteins represents a promising strategy for the exploration and understanding of protein structure and function. The ultimate goal of using such molecules is the modulation of protein function through controlled interference with the underlying binding events. In addition to their basic significance, such proteinmimetics are also useful tools for a range of biomedical applications, in particular the inhibition of disease-associated protein-ligand interactions. Owing to their chemical and structural relation to proteins, as well as the relative simplicity of their chemical or recombinant synthesis, peptides have emerged as adequate molecules for the mimicry of protein-binding sites, as well as the inhibition of protein-protein interactions.

• RNA folding and ribosome assembly.

  Authors: Sarah A Woodson

  Current opinion in chemical biology.

  Ribosome synthesis is a tightly regulated process that is crucial for cell survival. Chemical footprinting, mass spectrometry, and cryo-electron microscopy are revealing how these complex cellularRibosome synthesis is a tightly regulated process that is crucial for cell survival. Chemical footprinting, mass spectrometry, and cryo-electron microscopy are revealing how these complex cellular machines are assembled. Rapid folding of the rRNA provides a platform for protein-induced assembly of the bacterial 30S ribosome. Multiple assembly pathways increase the flexibility of the assembly process, while accessory factors and modification enzymes chaperone the late stages of assembly and control the quality of the mature subunits.

• Following polypeptide folding and assembly with conformational switches.

  Authors: Kevin Pagel, Beate Koksch

  Current opinion in chemical biology.

  Conformational transitions are a crucial factor in the vast majority of protein misfolding diseases. In most of these cases, the change in conformation is accompanied by the formation of insolubleConformational transitions are a crucial factor in the vast majority of protein misfolding diseases. In most of these cases, the change in conformation is accompanied by the formation of insoluble aggregates, which often precludes a detailed characterization at the molecular level. Therefore, much effort has been put into the development of simplified, easy-to-synthesize peptide models that can be used to elucidate the molecular processes that underlie the conformational switch. For a design to be successful, two, sometimes concomitantly fulfilled, requirements are of importance. First, it is essential to create inherent structural ambiguity. This is usually achieved by combining the most prominent characteristics of different folds within a consensus sequence. Second, a stimulus-sensitive functionality that responds to alterations in the environment, such as pH, ionic strength or the presence of metal ions, is often needed to control structural conversion and to shift the equilibrium in either direction.

• Structured non-coding RNAs and the RNP Renaissance.

  Authors: J Robert Hogg, Kathleen Collins

  Current opinion in chemical biology.

  Non-protein-coding (nc) RNAs are diverse in their modes of synthesis, processing, assembly, and function. The inventory of transcripts known or suspected to serve their biological roles as RNA hasNon-protein-coding (nc) RNAs are diverse in their modes of synthesis, processing, assembly, and function. The inventory of transcripts known or suspected to serve their biological roles as RNA has increased dramatically in recent years. Although studies of ncRNA function are only beginning to match the pace of ncRNA discovery, some principles are emerging. Here we focus on a framework for understanding functions of ncRNAs that have evolved in a protein-rich cellular environment, as distinct from ncRNAs that arose originally in the ancestral RNA World. The folding and function of ncRNAs in the context of ribonucleoprotein (RNP) complexes provide myriad opportunities for ncRNA gain of function, leading to a modern-day RNP Renaissance.

• Energy barriers, pathways, and dynamics during folding of large, multidomain RNAs.

  Authors: Inna Shcherbakova, Somdeb Mitra, Alain Laederach, Michael Brenowitz

  Current opinion in chemical biology.

  Large, multidomain RNA molecules are generally thought to fold the following multiple pathways down rugged landscapes populated with intermediates and traps. A challenge to understanding RNA foldingLarge, multidomain RNA molecules are generally thought to fold the following multiple pathways down rugged landscapes populated with intermediates and traps. A challenge to understanding RNA folding reactions is the complex relationships that exist between the structure of the RNA and its folding landscape. The identification of intermediate species that populate folding landscapes and characterization of elements of their structures are the key components to solving the RNA folding problem. This review explores recent studies that characterize the dominant pathways by which RNA folds, structural and dynamic features of intermediates that populate the folding landscape, and the energy barriers that separate the distinct steps of the folding process.

• Fluorescent probes for bioimaging applications.

  Authors: Takuya Terai, Tetsuo Nagano

  Current opinion in chemical biology.

  Fluorescent probes based on small organic molecules have become indispensable tools in modern biology because they provide dynamic information concerning the localization and quantity of theFluorescent probes based on small organic molecules have become indispensable tools in modern biology because they provide dynamic information concerning the localization and quantity of the molecules of interest, without the need of genetic engineering of the sample. In this review, following a brief outline of the principle of fluorescence imaging, we recount some recent achievements in the field of small-molecular fluorescent probes. First, probes for metal cations, including those suitable for two-photon imaging, are introduced. Next, methodologies to visualize proteases are discussed, with special emphasis on activity-based probes for use in vivo. All these probes have been confirmed to be applicable to cellular or in vivo imaging.

• Measurement science: the engine of chemical biology.

  Authors: Shana O Kelley, David R Walt

  Current opinion in chemical biology.

• Small-molecule catalysts of oxidative protein folding.

  Authors: Watson J Lees

  Current opinion in chemical biology.

  Oxidative protein folding occurs both in vivo and in vitro and involves the formation and rearrangement of protein disulfide bonds (SS bonds). In vivo these reactions are catalyzed by enzymes,Oxidative protein folding occurs both in vivo and in vitro and involves the formation and rearrangement of protein disulfide bonds (SS bonds). In vivo these reactions are catalyzed by enzymes, including the eukaryotic enzyme protein disulfide isomerase (PDI). Using the physical properties of PDI as a guide, several small-molecule catalysts of oxidative protein folding have been designed, synthesized, and tested. These small molecules can improve the folding rate of the model substrate ribonuclease A by a factor of over 10 and improve the yield by up to a factor of 3 over traditional conditions. The molecules have also been demonstrated to significantly improve the in vivo folding of proteins as well.

• Electron transfer in peptides and proteins.

  Authors: Bernd Giese, Michael Graber, Meike Cordes

  Current opinion in chemical biology.

  Proteins and peptides use their amino acids as medium for electron-transfer reactions that occur either in single-step superexchange or in multistep hopping processes. Whereas the rate of theProteins and peptides use their amino acids as medium for electron-transfer reactions that occur either in single-step superexchange or in multistep hopping processes. Whereas the rate of the single-step electron transfer dramatically decreases with the distance, a hopping process is less distance dependent. Electron hopping is possible if amino acids carry oxidizable side chains, like the phenol group in tyrosine. These side chains become intermediate charge carriers. Because of the weak distance dependency of hopping processes, fast electron transfer over very long distances occurs in multistep reactions, as in the enzyme ribonucleotide reductase.

• Nanowire sensors for multiplexed detection of biomolecules.

  Authors: Bo He, Thomas J Morrow, Christine D Keating

  Current opinion in chemical biology.

  Nanowire-based detection strategies provide promising new routes to bioanalysis that could one day revolutionize the healthcare industry. This review covers recent developments in nanowire sensorsNanowire-based detection strategies provide promising new routes to bioanalysis that could one day revolutionize the healthcare industry. This review covers recent developments in nanowire sensors for multiplexed detection of biomolecules such as nucleic acids and proteins. We focus on encoded nanowire suspension arrays and semiconductor nanowire-based field-effect transistors. Nanowire assembly and integration with microchip technology is emphasized as a key step toward the ultimate goal of multiplexed detection at the point of care using portable, low power, electronic biosensor chips.

• Chemistry's prodigal child: enzyme mechanism.

  Authors: Gideon J Davies, James H Naismith

  Current opinion in chemical biology.

• Nano-Biophotonics: new tools for chemical nano-analytics.

  Authors: Thomas Huser

  Current opinion in chemical biology.

  The nondestructive chemical analysis of biological processes in the crowded intracellular environment, at cellular membranes, and between cells with a spatial resolution well beyond the diffractionThe nondestructive chemical analysis of biological processes in the crowded intracellular environment, at cellular membranes, and between cells with a spatial resolution well beyond the diffraction limit is made possible through Nano-Biophotonics. A number of sophisticated schemes employing nanoparticles, nano-apertures, or shaping of the probe volume in the far field have significantly extended our knowledge about lipid rafts, macromolecular complexes, that is, chromatin, vesicles, and cellular organelles, and their interactions and trafficking within the cell. Here, I review some of the most recent developments in Nano-Biophotonics that already are or soon will become relevant to the analysis of intracellular processes. The pros and cons of the various techniques will be discussed and an outlook of their prospects for the near future will be provided.

• Folding and unfolding single RNA molecules under tension.

  Authors: Michael T Woodside, Cuauhtémoc García-García, Steven M Block

  Current opinion in chemical biology.

  Single-molecule force spectroscopy constitutes a powerful method for probing RNA folding: It allows the kinetic, energetic, and structural properties of intermediate and transition states to beSingle-molecule force spectroscopy constitutes a powerful method for probing RNA folding: It allows the kinetic, energetic, and structural properties of intermediate and transition states to be determined quantitatively, yielding new insights into folding pathways and energy landscapes. Recent advances in experimental and theoretical methods, including fluctuation theorems, kinetic theories, novel force clamps, and ultrastable instruments, have opened new avenues for study. These tools have been used to probe folding in simple model systems, for example, RNA and DNA hairpins. Knowledge gained from such systems is helping to build our understanding of more complex RNA structures composed of multiple elements, as well as how nucleic acids interact with proteins involved in key cellular activities, such as transcription and translation.

• Peptoid architectures: elaboration, actuation, and application.

  Authors: Barney Yoo, Kent Kirshenbaum

  Current opinion in chemical biology.

  Peptoids are peptidomimetic oligomers composed of N-substituted glycine units. Their convenient synthesis enables strict control over the sequence of highly diverse monomers and is capable ofPeptoids are peptidomimetic oligomers composed of N-substituted glycine units. Their convenient synthesis enables strict control over the sequence of highly diverse monomers and is capable of generating extensive compound libraries. Recent studies are beginning to explore the relationship between peptoid sequence, structure and function. We describe new approaches to direct the conformation of the peptoid backbone, leading to secondary structures such as helices, loops, and turns. These advances are enabling the discovery of bioactive peptoids and will establish modules for the design and assembly of protein mimetics.

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