bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptide Combinatorial Libraries
Authors: Liu Ruiwu , Lam Kit S. 
Published: February 2008

Abstract
Peptide libraries, which consist of a few thousands to tens of millions of distinct peptides, can be generated combinatorially through biologic or synthetic approaches. The phage‐display peptide library method is simple and economical, and peptides with various natural protein folds can be generated by this approach; but this biologic method generally is limited to peptides that contain only L‐amino acids. Synthetic combinatorial libraries, however, can accommodate D‐amino acids, unnatural amino acids, and even organic moieties, which makes these approaches highly versatile. These synthetic methods include the spatially addressable parallel library method, the combinatorial library method that requires deconvolution, the one‐bead one‐compound (OBOC) combinatorial library method, the self‐assembled peptide nucleic acid (PNA) encoded chemical microarrays, and the synthetic library method that requires chromatography selection. Various methods to screen these combinatorial libraries have been developed. For example, phage‐display peptide libraries can be screened for the ability of phages to bind to unique immobilized target proteins or whole cells, peptide microarrays can be screened for their ability to interact with fluorescent proteins, combinatorial library methods that require deconvolution can be screened by standard solution‐phase assays, and OBOC libraries can be screened by on‐bead binding or functional assays or several solution‐phase cell‐based or biochemical assays. Combinatorial peptide library methods are enabling technologies that have proven to be very useful in basic research and drug discovery.
Photosynthesis: Electron Transfer Chemistry
Authors: van der Est Art 
Published: February 2008

Abstract
In oxygenic photosynthesis, light‐induced electron transfer reactions occur in two photosystems embedded in the thylakoid membrane. These complexes bind many cofactors and are among the handful of membrane proteins for which the X‐ray crystal structures have been determined. The availability of this structural information, in combination with advanced spectroscopic techniques, has allowed the electron transfer reactions to be studied in detail. This work has revealed the pathways, rates, and yields of the electron transfer reactions but has also raised several intriguing questions about how these properties are governed by the protein–cofactor interactions. In this article, a brief overview of the main features of these very complex reactions is given, along with a summary of some techniques used to study them. A short survey of some recent advances in our understanding of the chemistry of electron transfer in photosynthesis is given.
Polyketide Biosynthesis: Polyethers
Authors: Hill Alison M. 
Published: February 2008

Abstract
This review covers the biosynthesis of terrestrial and marine polyethers and discusses their biologic properties and the molecular genetics and enzymology of the proteins responsible for their formation. The biosynthesis of monensin, nanchangmycin, nonactin, and the marine polyether ladders are discussed in detail. Novel enzymes found only in type I polyketide polyether gene clusters that are responsible for the epoxidation and cyclization of polyene biosynthetic intermediates are described. The macrotetrolide biosynthetic gene cluster, which is an ACP‐less type II polyketide synthase that functions noniteratively is reviewed.
Post‐Translational Modifications to Regulate Protein Function
Authors: Lin Hening , Du Jintang , Jiang Hong 
Published: February 2008

AbstractProtein post‐translational modifications (PTM) are very important to regulate protein function and to control numerous important biological processes. Here a brief review of commonly found enzyme‐catalyzed PTM is given. These PTM include modifications that occur on protein side chains and those that involve protein backbones. The introduction of different PTM is followed by a summary of the molecular basis for the regulation of protein function by PTM. The focus is then given to a few major PTM that play important roles in eukaryotes, such as phosphorylation, methylation, acetylation, glycosylation, ubiquitylation, and proteolysis. For each modification, a description will be given about the residues modified, the enzymatic reaction mechanisms, the major known biological functions, and its relevance to human diseases. At the end, we discuss challenges in identifying new pathways regulated by known PTM and discovering new PTM.
Protease Inhibitors: Mechanisms
Authors: Farady Christopher J. , Craik Charles S. 
Published: February 2008

AbstractRelatively few design principles underlie the mechanisms of inhibition of a myriad range of protease inhibitors. Protease inhibitors tend to be competitive and to compete with substrate binding, either through direct competition or deformation of the protease active site. Although protein inhibitors can gain potency through the burial of a large surface area and specificity through contacts with specific exosites, small‐molecule inhibitors primarily gain potency through interactions with the catalytic machinery of the enzyme and specificity through interactions with the substrate binding sites. Incorporation of these design principles into chemical probes and drugs have improved greatly our ability to create potent and specific protease inhibitors.
Amyloid Formation
Authors: Abedini Andisheh , Raleigh Daniel P 
Published: February 2008

AbstractAmyloids are β‐sheet rich fibrillar protein structures that result from the self‐assembly of polypeptides and proteins. A wide range of proteins are known to form amyloid fibrilsin vivoand an even larger number do soin vitro. More than 20 different human diseases involve amyloid formation, and the amyloid fibril or intermediates populated during its assembly are cytotoxic. All amyloid fibrils share common structural features despite exhibiting considerable variation in primary sequence. These features include a crossed β‐sheet organization in which the individual β‐strands are arranged perpendicular to the fiber axis such that the hydrogen bonds are oriented parallel to the fibril axis, resistance to proteolysis, and the ability to bind to certain dyes. Normally, the aggregation of proteins into amyloid is a pathological event; however, evidence indicates that naturally occurring amyloids may also play a beneficial biological rolein vivo.
RNA
Interference: Mechanisms and Proteins Involved
Authors: Wang Wang‐Xia , Nelson Peter T. , Tang Guiliang 
Published: February 2008

Abstract
RNA interference (RNAi) and microRNA (miRNA) pathways participate in posttranscriptional gene expression regulation. RNAi and miRNA biochemistry involve short (∼22 nucleotide) regulatory RNAs: small interfering RNA (siRNA) and miRNA. Both siRNAs and miRNAs guide RNA–protein complexes to “target” complementary messenger RNAs (mRNAs) for cleavage or translational repression. Many proteins involved in these pathways have been elucidated. The biochemical mechanisms of miRNA/siRNA processing have been dissected in detail in plants and in animals using biochemical and genetic approaches. Here we review the current literature on RNAi and miRNA mechanisms with a special focus on the protein components.
Pre‐mRNASplicing
Authors: Karijolich John , Yi‐Tao Yu 
Published: February 2008

AbstractPre‐mRNA splicing is an RNA processing reaction by which introns are removed from an mRNA precursor and exons are precisely joined together to form a functional mature mRNA. Splicing involves two successivetrans‐esterification reactions that occur in the spliceosome, which is a multicomponent complex composed of a large number of protein factors and five small nuclear RNAs (snRNAs), each functioning as an RNA–protein complex (ribonucleoprotein or snRNP). A significant body of evidence indicates that both spliceosome assembly and catalytic core formation are orchestrated by an intricate network of RNA–RNA interactions. Most eukaryotic introns invariably start with the dinucleotide GT (GU in RNA) and end with the dinucleotide AG. Splicing of these introns occurs in the major spliceosome containing five abundant snRNPs (U1, U2, U4, U5, and U6). In high eukaryotes, a rare class of introns also exists, beginning with the dinucleotide AT (AU in RNA) and ending with the dinucleotide AC. Removal of this class of introns requires the participation of a different set of snRNPs, namely U11, U12, U5, U4atac, and U6atac. Recent advances in pre‐mRNA splicing have provided strong evidence for an RNA enzyme catalyzing the twotrans‐esterification reactions in the spliceosome.
RNAStability: Chemistry, Measurement and Modulation
Authors: McDowall Kenneth J. 
Published: February 2008

AbstractMolecules composed of RNA perform many roles that are vital for the life and reproduction of all cellular organisms and viruses, one of which is the role of messengers that carry from genes the information required for the production of protein. A typical feature of messenger RNA (mRNA) is its relative instability, which ensures that the production of any particular protein soon comes to an end when it is no longer required and synthesis of the message is downregulated. Moreover, while a transcript is being produced, its rate of decay is as important as its rate of synthesis in determining its cellular concentration and thus, to a large extent, its level of function. The turnover of mRNA, and indeed all other types of RNA, is mediated by multiple ribonucleases. The activity of these enzymes in cells can be inhibited rapidly by chemical treatments; thus, for many experimental systems their presence does not pose a significant barrier to the study of gene regulation at the RNA level. However, the development of RNA‐based therapeutics such as small interfering RNAs and aptamers has required the introduction of modifications to prevent their degradation by ribonucleases within the cells and body fluids of humans. This article describes the properties of RNA that make it susceptible to ribonucleases and the techniques used to determine the stability of RNA molecules. It also provides examples of how RNA stability in livings cells is being modulated for biotechnology and clinical applications, and it reviews the strategies that are being adopted to increase thein vivostability of RNAs with therapeutic potential.
Symbiosis, Chemical Biology of
Authors: Flachshaar Daniel , Piel Jörn 
Published: February 2008

AbstractThe term “symbiosis” was defined by Anton de Bary in his monograph “Die Erscheinung der Symbios” as “the living together of unlike organisms” (1). His studies were based on the formation of lichens, which are the result of an association between a fungus and an alga or cyanobacterium. The definition was coined in the end of the nineteenth century but is regarded by most symbiosis researchers as largely valid today. Accordingly, any specific association between two or more species can be classified as symbiosis. It should be noted that many scientists use symbiosis in a more restricted way to denote a mutually beneficial relationship. This article will give an overview of various biologic manifestations of symbiosis and discuss selected examples, where primary or secondary metabolites play a crucial role in the association. If the partners in a symbiosis differ in size, the larger member is termed “host” and the smaller member is termed “symbiont” or “symbiote.” The more common term “symbiont” will be used here. One general way to distinguish between various forms of symbiosis is to identify the location of the attachment of the symbiont to the host. Symbionts that live on the host surface, including internal surfaces like the digestive tube, participate in ectosymbiosis (Greek: ɛκτoς = outside). If a symbiont is localized within the tissues of the host, the association is termed “endosymbiosis” (Greek: ɛνδoν = within). Endosymbionts can be found either in the extracellular space or intracellularly.
Unnatural Amino Acids to Investigate Biological Processes
Authors: Johnson David B.F. , Takimoto Jeffrey K. , Xu Jianfeng , Wang Lei 
Published: February 2008

AbstractTo circumvent the constraint imposed by the 20 canonical amino acids on the study of protein structure and function, various chemical and biosynthetic methods have been developed to incorporate unnatural amino acids into proteins. Unnatural amino acids now can be genetically encoded in living cells in a manner similar to that of common amino acids, which expands site‐directed mutagenesis to diverse novel amino acids. The use of unnatural amino acids grants researchers a multitude of chemical and physical properties that cannot be found in the normal genetic repertoire, which significantly improves their ability to manipulate proteins and protein‐involved biologic processes. Changes have been tailored into proteins to accurately dissect the contribution of hydrogen bonding, hydrophobic packing, cation‐π interaction, and entropy to protein stability, as well as to precisely examine the structural and functional role of crucial residues. Unnatural amino acids also enable the introduction of new chemical reactivities, biophysical probes, mock posttranslational modifications, photoactive groups, and numerous other functionalities for the modification and regulation of protein activities. These studies not only reveal fundamental information of protein structure and function but also explore new means for generating novel protein properties and controlling biologic events.
Taste, Chemical Biology of
Authors: Behrens Maik , Stähler Frauke , Shi Peng , Bufe Bernd , Meyerhof Wolfgang 
Published: February 2008

Abstract
The mammalian sense of taste is crucial for evaluating food palatability and nutritional quality. To achieve the detection of relevant chemicals, evolution has shaped a set of receptor molecules that allow the detection of five basic taste qualities: sweet, umami, bitter, salty, and sour. Each taste modality has unique characteristics and serves a distinct function for an animal's nutrition. Therefore, we address the characteristics, the recent advances, the persisting difficulties, and the future perspectives of the basic taste qualities in separate paragraphs. Enormous progress has been made in the identification and the characterization of taste receptor molecules, and in the growing number of animal genomes accessible from databases, which has inspired us to devote a section of this review to discuss a series of sophisticated evolutionary studies on taste receptor molecules. Finally, evidence is accumulating to show that taste receptor and signal transduction molecules have nongustatory functions as well. The extragustatory expression of such genes and the resulting implications are summarized in the final section.
Plant Terpenoids
Authors: Keeling Christopher I. , Bohlmann Jörg 
Published: February 2008

Abstract

Terpenoids are the largest class of all known natural products. Plants produce a variety of terpenoid compounds that number in the thousands. Some terpenoids are involved in plant growth and development directly (i.e., in primary metabolism), but most plant terpenoids are thought to function in interactions of plants with their biotic and abiotic environment and have traditionally been referred to as secondary metabolites. In addition to the isolation and identification of plant terpenoids, research has concentrated on the biosynthesis, the biological function, and the exploitation of plant terpenoids for human use as biomaterials and pharmaceuticals. Plant terpenoids are biosynthesized from C
5
precursors by the action of prenyl transferases and terpenoid synthases. Often, terpenes are acted on by cytochromes P450 and other enzymes to increase their functionalization. Terpenoid biosynthesis in plants involves several subcellular compartments. The accumulation of terpenoids requires efficient transport systems and specialized anatomical structures. Using isoprene (a hemiterpene), menthol (a monoterpene), artemisinin (a sesquiterpene), and paclitaxel [better known under the registered trademark Taxol (Bristol Myers Squibb, New York)] and diterpene resin acids (diterpenes) as examples, we highlight some strategies, techniques, and results of plant terpenoid research with a strict focus on the low‐molecular‐weight (C
5
–C
20
) terpenoids of specialized plant metabolism.
Transcript Profiling Tools
Authors: Wirta Valtteri , Lundeberg Joakim 
Published: February 2008

AbstractRegulation of gene expression plays a central role in controlling and shaping the functions of a cell. Tools for quantification of the expression of individual genes have been available for years; but over the past decade, development of the microarray technology and accompanying bioinformatics tools has made it possible to generate comprehensive overviews of the transcriptional events in both diseased and normal cells and tissues. This review covers various approaches for transcript profiling from single genes to more global analyzes approaches. In addition, a detailed description of different microarray‐based technology platforms will be provided, which all enable an essentially genome‐wide characterization of the transcript levels. We also discuss the current challenges and future trends within transcriptional profiling, and we introduce briefly the next generation DNA sequencing technology that will enable a more detailed description of the entire transcriptome, which includes various small RNA species (e.g., microRNA) and other noncoding transcripts.
Transcription‐Based Therapeutics
Authors: Wands Amberlyn M. , Mapp Anna K. 
Published: February 2008

Abstract
Aberrant transcription patterns are associated with most human diseases. Therefore, enormous interest exists in the development of designer molecules that can be used to regulate directly the transcription of predetermined genes for the ultimate treatment of a wide range of disease states. One emerging strategy is to identify molecules that reconstitute one or more functions of the endogenous proteins that upregulate transcription, transcriptional activators. In doing so, they function as either inhibitors or activators of transcription. Using this approach, a variety of protein‐ and small molecule‐based transcriptional regulators have been developed, and at least one has reached clinical trials.
Methylerythritol Phosphate Pathway for Formation of Isoprene Units
Authors: Rohmer Michel 
Published: February 2008

AbstractThe carbon skeleton of isoprenoids is derived from the branched C5skeleton of isoprene. Isopentenyl diphosphate and dimethylallyl diphosphate represent the biologic equivalents of isoprene. From research on cholesterol biosynthesis in liver tissues and on ergosterol in yeast, mevalonate was accepted as the universal precursor of isoprenoids. However this assertion is inaccurate. Incorporation of labeled acetate and glucose isotopomers into bacterial isoprenoids and into diterpenes of ginkgo embryos indicated fortuitously the existence of an alternative mevalonate‐independent route. Its full elucidation required experiments using13C‐ and2H‐labeled precursors followed by extensive nuclear magnetic resonance analyses as well as a combination of biochemical and molecular biology methods. These additional studies revealed a complete set of novel unsuspected enzymes.
Click Peptides: Design and Applications
Authors: Kiso Yoshiaki , Taniguchi Atsuhiko , Sohma Youhei 
Published: February 2008

Abstract

A “click peptide” is a chemically modified peptide analog used to understand the biologic function of peptides. A click peptide does not exhibit the inherent biologic activity of the original peptide because of a simple chemical modification of the peptide backbone and; by adding an exogenous action (“click”) such as pH‐change or photo‐irradiation, easily affords the native peptide in situ with a quick and easy one‐way conversion via a native amide bond‐forming reaction. For example, the designed click peptides of Alzheimer's amyloid β peptide (Aβ) 1–42, which did not exhibit a self‐assembling nature because of a backbone isomerization from a native Gly
25
‐Ser
26
bond to a β‐ester bond, could migrate to the intact Aβ1‐42 under physiologic conditions by pH‐ or photo‐triggered “click” via an
O
→
N
intramolecular acyl migration reaction. This click peptide overcomes the difficulties in handling Aβ1‐42 in syntheses and biologic experiments, which clarifies the currently unexplained processes of Alzheimer's disease.
Lead Optimization in Drug Discovery
Authors: Lindsley Craig W. , Weaver David , Bridges Thomas M. , Phillip Kennedy J. 
Published: February 2008

AbstractLead optimization in drug discovery has changed significantly over the past five years and no longer is fragmented into separate hit‐to‐lead and lead optimization phases. Chemical lead optimization from high‐throughput screening (HTS) to clinical candidate identification is now one seamless process that draws on new technologies for accelerated synthesis, purification, and screening of directed, iterative compound libraries. Advances In high‐throughput screening technologies allow detection of new allosteric modes of target modulation, which provides new chemotypes and target opportunities. With the incorporation of drug metabolism and pharmacokinetics (DMPK) inputs early in the lead optimization work flow, molecules are not optimized solely for target potency and selectivity. Moreover, “closed‐loop” work flows are in place such that synthesis and primary screening operate on a 1‐week turnaround for up to 48 compounds/week with DMPK data cycling every other week to guide compound design, which provides expedited timelines for the development of proof‐of‐concept compounds and clinical candidates with limited human resources.
DNATransposition
Authors: Rousseau Philippe , Chandler Michael 
Published: February 2008

AbstractDNA transposable elements are a ubiquitous and highly diverse group of mobile genetic elements capable of moving within and between genomes. Despite their diversity, only a limited number of chemical mechanisms, which are catalyzed by enzymes called transposases, are used to promote this movement. DNA transposases can be classified according to these chemistries. We outline present knowledge that concerns the mechanisms adopted by the five different types of transposase identified to date: the DDE‐, Y‐, S‐, Y2‐, and Y1‐transposases. The DDE and Y1 enzymes are perhaps the best characterized, whereas the data available for the Y‐ and S‐transposases suggest that they use similar mechanisms to their closely related cousins, the Y‐ and the S‐ site‐specific recombinases.
Saliva in Health and Disease, Chemical Biology of
Authors: Fábián Tibor K. , Fejérdy Pál , Csermely, Péter 
Published: February 2008

Abstract
Saliva is a bodily fluid secreted by three pairs of major salivary glands (parotid submandibular and sublingual) and by many of minor salivary glands. Saliva is supplemented with several constituents that originate from blood serum, from intact or destroyed mucosal and immune cells, and from intact or destroyed oral microorganisms that result in a complex mixture of a variety of molecules. Saliva plays an important role in acquired pellicle formation on tooth surfaces, crystal growth homeostasis, bacterial adhesion, plaque formation, and—because of its lubricating effect—in maintaining mucosal integrity of the oral and upper gastrointestinal mucosal surfaces. It also plays an important role in physico‐chemical defense, antimicrobial defense, and wound healing. Many saliva constituents including proteins, carbohydrates, lipids, and ions interact under fine regulation to fulfill these important tasks. Local and systemic disorders may disturb and interrupt these complex balanced functions, which can lead to mucosal and tooth damages. In other cases, systemic disorders induce salivary changes without any significant local effects. Many such changes are of high diagnostic interest because they can be rather specific to the causing conditions and can be used for screening and early diagnosis of several local and systemic disorders.