bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic Synthesis of Carbohydrate‐Containing Biomolecules
Authors: Yu Hai , Chen Xi
Published: February 2008

As important biomolecules in living organisms, carbohydrates have received increasing attention in recent years. Their important roles in biologic events are being continuously unraveled. The development of synthetic methodologies, including both chemical and enzymatic methods, contributes greatly to the advance of the field of glycoscience. The involvement of regio‐ and stereo‐selective enzymes in the synthesis of complex carbohydrate‐containing molecules has become an indispensable approach. Many enzymes involved in the biosynthesis and biodegradation of carbohydrates have been characterized and have been applied for the production of carbohydrate‐containing biomolecules, including oligosaccharides, polysaccharides, glycoproteins, glycolipids, and glycosylated natural products. A range of strategies for enzymatic synthesis have also been developed, such as protein engineering of glycosidases and glycosyltransferases by site‐directed mutagenesis or directed evolution, one‐pot multiple‐enzyme synthesis, sugar nucleotide regeneration, solid‐phase enzymatic synthesis, synthesis using immobilized enzymes, and cell‐based synthesis. Enzymatic synthesis will continue to play critical roles in obtaining complex carbohydrate‐containing biomolecules. Future efforts should focus on identifying synthetically useful enzymes such as those with flexible or novel substrate specificity and those that can form new bonds. This identification can be achieved by functional genomics and mutagenesis studies. Development of novel enzymatic synthetic methods is also critical to access diverse naturally occurring and non‐natural derivatives of carbohydrates and glycoconjugates.
Fluorescence Spectroscopy: Applications in Chemical Biology
Authors: Sapsford Kim E. , Berti Lorenzo , Medintz Igor L.
Published: February 2008

Fluorescence spectroscopy in all of its variations can be considered among the most powerful types of analysis available to chemical biology. However, to be useful almost all applications are dependent on optimal labeling of biomolecules with a fluorophore and on the appropriate choice of analytical technique. In this article, we examine the applications and contributions of fluorescent spectroscopy to chemical biology in three inter‐related sections. We first examine the properties of the common fluorophores available from many disparate structural and functional classes, which includes a discussion of their individual benefits and liabilities in the context of their application. The available conjugation chemistries used to attach fluorophores to myriad biomolecules are next reviewed. As each class of biomolecule differs in both structure and function, the focus here is on strategies for the specific labeling of different functional groups. Last, some major types of fluorescent spectroscopy and the associated biologic questions and analysis that can be addressed with them are covered briefly.
Fluorescence Techniques for Proteins
Authors: Johnson Carey K.
Published: February 2008

Biologists and chemists are increasingly turning to fluorescence to investigate proteins. Not only is fluorescence detection highly sensitive, but it can also report specific information about a range of properties of proteins. For example, fluorescence can be used to probe the environment of fluorescent molecules, interactions with other proteins, and the motions of proteins over time scales from picoseconds to seconds. This article surveys the properties of biologic fluorophores that can be used to study proteins and introduces the fluorescence techniques commonly applied to proteins, with an emphasis on the information generated. Techniques discussed include steady‐state emission, time‐resolved detection, fluorescence anisotropy or depolarization, energy transfer, fluorescence correlation spectroscopy, single‐molecule spectroscopy, and fluorescence imaging.
Hemes in Biology
Authors: Ortiz de Montellano Paul R.
Published: February 2008

Heme (iron protoporphyrin IX) is a fundamental factor in biology with many physiologic roles. Its biosynthesis and degradation are regulated tightly because heme in excess of that required for incorporation into the available apoproteins is toxic. Heme itself is the dominant form in biology, but it is modified additionally to satisfy specific biochemical requirements. Both the biosynthesis of heme and its distribution into the various compartments of the cell and organism require the intervention of heme transporters. In contrast to the passive transport afforded by proteins like albumin, the transfer of heme across membranes is mediated by energy‐dependent transporters. One role of heme is to function as a regulatory molecule whose concentration controls the translational expression of multiple genes directly. As the prosthetic group of receptors that respond to oxygen, nitric oxide (NO), and other iron ligands, it is also involved in signaling. Finally, it is the prosthetic group of diverse families of hemoproteins, including the globins, cytochromes, P450 monooxygenases, NO synthases, dioxygenases, peroxidases, peroxygenases, and catalases.
Hormone Signaling
Authors: Weatherman Ross V.
Published: February 2008

Hormone signaling has always been a field that has required working at the chemistry–biology interface. The development of new chemical tools plays a major role in understanding the molecular mechanisms of hormone signaling and the physiologic outcomes of hormone receptor action. This article will outline the relevance of molecular endocrinology to the field of chemistry and the use of chemical approaches to solving problems in hormone research. The basic biologic outline of a hormone signaling system and the different classes of hormone molecules and their receptors will be discussed. In addition, several research areas in which new chemical tools have been playing key roles will be described in more detail, including the discovery of ligands for orphan hormone receptors, the development of non‐natural hormone receptor mimics, and the use of selective hormone receptor modulators to understand the role of specific hormone receptor signaling pathways. Hormone signaling systems that will be discussed include the thyronamines and trace amine receptor, the liver X and farnesol X receptors, small molecules capable of binding to peptide hormone receptors, the melanocortin receptor family, the estrogen receptor, and chemically orthogonal hormone receptor–ligand pairs. Major challenges facing the field as well as some different experimental methods used to study hormone signaling will also be discussed.
Hydration Forces
Authors: Todd Brian A. , Sidorova Nina Y. , Rau, Donald C. , Stanley Christopher
Published: February 2008

Force measurements on a wide variety of biologic macromolecules indicate that the perturbation of water structuring as hydrated surfaces closely approach can dominate interaction energetics. Forces with remarkably similar characteristics are observed for the repulsive interactions of charged polymer surfaces, of uncharged polymer surfaces, of charged solutes with uncharged surfaces, and of uncharged solutes with charged surfaces stressing the universality of the hydration force in aqueous solution. Repulsive interactions are caused by a disruption of the hydrogen bonding network of the intervening water between surfaces. The available measurements of forces between macromolecules that spontaneously assemble are consistent with an attractive hydration interaction. A water‐order parameter theory has been developed that is successful for predicting force curve behaviors. The direct involvement of water structuring in the interaction between macromolecules has important consequences for recognition, assembly, and conformational transitions that underlie biologic function.
Inorganic Chemistry in Biology
Authors: Bertini Ivano , Turano Paola
Published: February 2008

Several inorganic chemical elements play fundamental roles in biological processes. The contribution of inorganic chemistry to the understanding of biological processes is presented here from a historical perspective: from the first discoveries of metal ions in living organisms to the modern approaches of inorganic structural biology and bioinformatics, through the characterization of metal binding sites in proteins and in biomimetic model compounds. Definitions are provided for the fundamental concepts of metal cofactor, metalloprotein, and metalloenzyme.
Ion Channels in Medicine
Authors: Lehmann‐Horn Frank , Jurkat‐Rott Karin
Published: February 2008

Our current understanding of ion channels has been made possible by techniques such as electrophysiology and molecular biology, but genetics‐based approaches inspired by associated diseases have pointed to regions of functional significance on the ion channels. The ion channelopathies are caused by mutations of corresponding genes or autoantibodies. Although the channels form a highly diverse group (cation, anion, voltage‐gated, ligand‐gated) and are expressed in excitable and nonexcitable tissues, underlying mutations show recurrent patterns within functionally essential protein parts and lead to common clinical features and almost predictable mechanisms of pathogenesis. This knowledge will prove useful for development of treatment strategies for individuals with various genetic backgrounds and will contribute to both the effectiveness and safety of drugs in the future.
Iron‐Sulfur World
Authors: Wächtershäuser Günter
Published: February 2008

The theory of a chemo‐autotrophic origin of life in an Iron‐Sulfur World postulates quenched, aqueous flows of volcanic exhalations as sites for the emergence of the pioneer organism of life, which are characterized by a composite structure with an inorganic substructure and an organic superstructure. Iron, nickel, and other transition metal centers in the substructure are catalytic for the reductive formation of low‐molecular‐weight organic compounds by carbon fixation from volcanically derived carbonyl, cyano, sulfido, ammino, and other ligands. Some organic products become transition metal ligands instatu nascendiwith the effect of ligand‐accelerated autocatalysis as a chemical basis of pioneer reproduction, inheritance, and evolution. This unitary structure‐function relationship of the pioneer organism constitutes the “Anlage” for two major parallel strands of evolution, genetization, and cellularization, and the “mystery” of an increase of complexity throughout evolution is simply caused by the primal synthetic drive of the autotrophic pioneer organism that may well be persisting to this day.
Isoprostanes
Authors: Milne Ginger L. , Morrow Jason D.
Published: February 2008

The isoprostanes are a unique series of prostaglandin‐like compounds formedin vivovia a nonenzymatic mechanism involving the free radical‐initiated peroxidation of arachidonic acid. This article summarizes our current knowledge of these compounds. Herein, a historical account of their discovery and the mechanism of their formation are described. Methods by which these compounds can be analyzed and quantified are also discussed, and the use of these molecules as biomarkers ofin vivooxidant stress is summarized. In addition to being accurate indices of lipid peroxidation, some isoprostanes possess potent biological activity. This activity will be discussed in detail. Finally, in more recent years, isoprostane‐like compounds have been shown to be formed from polyunsaturated fatty acids, including eicosapentaenoic acid and docosahexaenoic acid. These findings will be summarized as well.
Kinases and Dephosphorylases: Chemistry and Roles
Authors: M. Ulrich Scott
Published: February 2008

Protein kinases and protein phosphatases catalyze phosphorylation and dephosphorylation of cellular proteins. Posttranslational protein phosphorylation is a major mechanism of signal transduction in eukaryotes; it serves as a reversible switch that alters the activity of target proteins as a means to link stimuli to the appropriate cellular response. In this article, I will review the structures and mechanisms of protein kinases and phosphatases as well as describe chemical tools developed to study protein phosphorylation.
Lantibiotics: Biosynthesis and Modes of Action
Authors: Furgerson‐Ihnken L.A. , van der Donk Wilfred A.
Published: February 2008

Lantibiotics are a unique class of antimicrobial peptides produced by Gram‐positive bacteria. They are synthesized ribosomally as precursor peptides and undergo extensive posttranslational modification to attain their biologically active structures. These modifications include dehydration of serine and threonine residues that produce dehydroalanines and dehydrobutyrines, followed by intramolecular addition of cysteine thiols to the unsaturated amino acids. The lantibiotic biosynthetic machinery displays low substrate specificity bothin vivoandin vitro, which allows for the engineering of novel lantibiotics. The polycyclic peptides exert their biological activity through several modes of action including the sequestration of the cell wall precursor lipid II and pore formation in bacterial membranes. Because of their high potency, several commercial applications of lantibiotics are being developed.
Essential Fatty Acids: Physiology and Clinical Significance
Authors: Das Undurti N.
Published: February 2008

Essential fatty acids (EFAs)—linoleic acid (LA) and α‐linolenic acid (ALA)—are essential for the brain growth and development of humans. EFAs are readily available in the diet, and hence their deficiency is not common. But, to provide their full benefit, EFAs have to be metabolized to their long‐chain metabolites. EFAs form precursors to various prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), lipoxins (LXs), resolvins, neuroprotectins, isoprostanes, and hydroxy‐ and hydroperoxyeicosa‐tetraenoates. Certain PGs, TXs, and LTs have pro‐inflammatory actions, whereas LXs, resolvins, and neuroprotectins are anti‐inflammatory in nature and are critical for wound healing, the resolution of inflammation, and the repair of tissues. EFAs and some of their long‐chain metabolites inhibit the activities of angiotensin‐converting and HMG‐CoA reductase enzymes and cholesteryl ester transfer protein (CETP), enhance acetylcholine levels in the brain, increase the synthesis of endothelial nitric oxide, augment diuresis, enhance insulin action, and could regulate telomerase activity. Thus, EFAs and their metabolites may function as an endogenous “polypill.” In addition, EFAs and their long‐chain metabolites react with nitric oxide (NO) to yield respective nitroalkene derivatives that exert cell‐signaling actions via ligation and activation of peroxisome proliferator‐activated receptors (PPARs). Thus, EFAs and their derivatives have varied biologic actions that may have relevance to their involvement in several physiologic processes and clinical conditions.
Lipid Signals: Extracellular
Authors: Chun Jerold , Dorris Helen L.
Published: February 2008

Lipid molecules can act as extracellular signals. They form a large and expanding class of influences on cellular and organismal homeostasis, which affect all organ systems and participate in many disease processes. Prominent members of this class include eicosanoids (e.g., leukotrienes or prostanoids like prostaglandins, protacyclins, and thromboxane), lysophospholipids (e.g., lysophosphatidic acid and sphingosine 1‐phosphate), endocannabinoids (e.g., anandamide and 2‐arachidonoylglycerol), ether lipids (e.g., platelet activating factor), and free fatty acids. These signals are in a dynamic steady state with structural phospholipids that make up the lipid membrane bilayer of all cells. Both distinct and shared enzymologies are involved in lipid signal biosynthesis and degradation. A dominant mechanistic theme for all
bona fide
extracellular lipid signals is their use of cognate 7‐transmembrane domain and G protein‐coupled receptors. Activation of these receptors causes myriad physiologic and pathophysiologic effects that encompass most aspects of cell biology and physiology. Studies on extracellular lipid signals have led to both mechanistic understanding and successful creation of useful medicines.
Lipidated peptide synthesis
Authors: Gerauer Marc , Koch Sebastian , Brunsveld Luc , Waldmann Herbert
Published: February 2008

In this review, an overview is given for the synthesis of lipidated peptides such as those belonging to the Rab, Ras, eNOS, and hedgehog proteins. The different approaches for the synthesis of specific lipidated peptides (palmitoylated, prenylated, and myristoylated) are discussed with special emphasis on solid‐phase synthesis methods, because these methods have turned out to be the preferred synthesis method for most required peptides. Different solid‐phase methods are described that are individually suited for different types of lipidated peptides, differing, for example, in lipidation pattern or amino acid side‐chain functionality and in their protein ligation functionality. For the described solution approaches, the block coupling strategies followed for the different lipidated peptides are highlighted. A special section in this review discusses the different synthetic tools for the incorporation of the lipid functionalities in the peptides. Although a generally validated strategy for the synthesis of lipidated peptides does not exist, because of the large number of different functionalities, this review aids in the conceptual design of synthetic protocols for lipidated peptides. Finally, the methods for the ligation of lipidated peptides to proteins are shortly discussed, as these methods also significantly influence the design and synthesis of lipidated peptides.
Mechanosensitive Channels
Authors: Martinac Boris
Published: February 2008

Mechanosensitive (MS) channels function as molecular transducers of mechanical forces into electrical and/or chemical intracellular signals in living cells. These channels play a major role in the physiology of mechanosensory transduction encompassing cellular processes that range from regulation of cellular turgor and growth in microorganisms to touch, hearing, and blood pressure regulation in vertebrates. Together with the recent work on MS channels in eukaryotic cells studies of prokaryotic MS channels using a multidisciplinary approach based on the patch‐clamp recording, X‐ray crystallography, computer simulations, and electronparamagnetic resonance and fluorescence resonance energy transfer spectroscopy, have significantly contributed to our understanding of the relationship between the structure and function in these membrane proteins. In particular, experiments employing chemical manipulation of the physical properties of the membrane lipid bilayer have shed light on 1) how MS channels detect physical forces in cellular membranes, and 2) what causes structural conformational changes in MS channels in response to membrane tension.
NAD(P) Dependent Dehydrogenases
Authors: Phillips Robert S.
Published: February 2008

NAD(P)H is the major carrier of reducing equivalents in cells. NAD(P)‐dependent dehydrogenases and reductases catalyze the reversible transfer of hydrogen equivalents between substrates and NAD(P). These enzymes include alcohol dehydrogenases, 2‐hydroxyacid dehydrogenases, aldehyde dehydrogenases, amino acid dehydrogenases, secondary amine dehydrogenases, disulfide oxidoreductases, transhydrogenases, azoreductases, sulfite and nitrite reductases, and phosphite dehydrogenase. NAD(P)‐dependent dehydrogenases are structurally diverse, but many contain a Rossmann fold for NAD(P) binding. Usually, alcohol dehydrogenases contain an essential metal ion cofactor that serves as a Lewis acid for substrate activation. However, most dehydrogenases use general acid/base catalysis to activate substrates for reaction. NAD(P)‐dependent dehydrogenases have been used in biocatalysis for stereoselective reductions of ketones and imines to give chiral alcohols and amines, respectively. Several important drug targets (e.g., dihydrofolate reductase) are NAD(P)‐dependent dehydrogenases.
Marine Natural Products: Chemical Diversity
Authors: Fusetani Nobuhiro
Published: February 2008

Oceans provide enormous and diverse habitats for marine life. The distinct feature of marine life is the domination of invertebrates, which account for more than 95% of marine animals. Most marine invertebrates are sessile and soft‐bodied and lack obvious physical defenses. Instead, they have evolved to defend by chemical means against predation and overgrowth by other fouling organisms. In fact, their secondary metabolites have unusual structural features and potent biologic activities, many of which are not found in terrestrial natural products. This review focuses on bioactive metabolites isolated mainly from marine invertebrates with a special emphasis on the uniqueness of marine natural products.
Plant‐Derived Natural Products Research: Recent Progress in Drug Discovery
Authors: Lee Kuo‐Hsiung , Itokawa Hideji , Akiyama Toshiyuki , Morris‐Natschke Susan L.
Published: February 2008

Numerous important bioactive compounds have been, and continue to be, isolated worldwide from natural sources. These compounds include both primary and secondary metabolites isolated mainly from plants, as well as from the animal and mineral kingdoms. The recent development of new bioassay methods has facilitated progress in the BDFI (bioactivity‐directed fractionation and isolation) of many useful bioactive compounds from natural sources (1). These active principles could be developed or additionally modified to enhance the biologic profiles as clinical trials candidates. Many natural pure compounds have become medicines, dietary supplements, and other useful commercial products. This article summarizes research on many different useful compounds isolated or developed from plants with an emphasis on those discovered recently by the laboratories of the authors as antitumor and anti‐HIV clinical trial candidates.
Neoglycoproteins, Chemistry of
Authors: Lee Yuan C.
Published: February 2008

Natural glycoproteins often contain heterogeneous oligosaccharide chains, which make it difficult to elucidate the structure–activity relationship of the carbohydrates of these glycoproteins. Neoglycoproteins were developed to overcome such a problem. Neoglycoproteins are proteins modified with carbohydrates of defined structures. The modification can be random or specific and can use chemical or enzymatic methods. The protein functional groups most often used are α/ɛ‐amino groups, β/γ‐carboxyl groups, γ‐carboxylamides, sulfhydrils, and phenols. In some cases, existing glycans on glycoproteins can be modified to make the glycan structures homogeneous. Alternatively, glycopeptides or glycoproteins can be synthesized totally
de novo
, without using any natural proteins, peptides, or oligosaccharides. In addition to providing homogeneous carbohydrate structures on a single protein, neoglycoproteins also provide a multivalency effect (glycoside clustering effect). The use of neoglycoproteins greatly promoted the understanding of the roles of carbohydrates in biologic systems, which led to some clinically important development.
Non‐Homologous Recombination
Authors: Wilson Thomas E.
Published: February 2008

Genetic recombination classically proceeds by the homologous recombination pathway, but direct joining of chromosome fragments lacking extensive homology also occurs and is of particular interest as a nearly ubiquitous genome alteration in cancer. At least two distinct but overlapping pathways of DNA repair are relevant to the execution of nonhomologous recombination: nonhomologous end joining (NHEJ) and microhomology mediated end joining (MMEJ). Like other DNA repair pathways, NHEJ and MMEJ seem to facilitate primarily genome maintenance, but by their nature are prone to errors, including an ability to join inappropriately paired chromosome break ends. This review considers the function of these pathways, with an emphasis on the unique and unusual biochemical properties of key enzymes, including DNA ligase IV and Pol X family DNA polymerases, and how these facilitate direct rejoining of broken chromosomes.
Nonribosomal Peptides: Biosynthesis
Authors: Schoenafinger Georg , A Marahiel Mohamed
Published: February 2008

Many microorganisms have evolved an unusual way of producing secondary peptide metabolites. Large multidomain enzymatic machineries, the so‐called nonribosomal peptide synthetases (NRPSs), are responsible for the production of this structurally diverse class of peptides with various functions, such as cytostatic, immunosuppressive, antibacterial, or antitumor properties. These secondary metabolites differ from peptides of ribosomal origin in several ways. Their length is limited to a mere 20 building blocks, roughly, and mostly a circular or branched cyclic connectivity is found. Furthermore, aside from the proteinogenic amino acids, a larger variety of chemical groups is found in these bioactive compounds: D‐configurated amino acids, fatty acids, methylated, oxidized, halogenated, and glycosylated building blocks. These functional and structural features are known to be important for bioactivity, and often natural defense mechanisms are thus evaded. In this article, we describe the enzymatic machineries of NRPSs, the chemical reactions catalyzed by their subunits, and the potential of redesigning or using these machineries to give rise to new nonribosomal peptide antibiotics.
Nucleic Acids: Chemical Damage
Authors: Friedberg Errol C. , Kodadek Thomas J.
Published: February 2008

Nucleic acids are highly reactive macromolecules that can undergo a variety of chemical changes that may be deleterious to their function. In particular, deoxyribonucleic acid (DNA) undergoes multiple spontaneous chemical changes and is reactive with reactive oxygen species generated during oxidative metabolism and with naturally occurring chemicals, ultraviolet radiation, and a myriad of environmental chemicals. This review highlights many of these chemical changes.
Olfaction, Chemical Biology of
Authors: Sell Charles S.
Published: February 2008

Smell is an intriguing sense in many ways. Although it is not the dominant sense in humans, it has affects on emotion and memory which can be very profound. Odor has long baffled chemists who try to model it in mechanistic terms, and a great deal of research has been invested in trying to understand how various features of molecular structure provide different odor characters and intensities. Many models for prediction of odor properties from chemical structure exist, but none are accurate and precise consistently. The reasons for this are now becoming clearer. The greatest breakthroughs in our understanding of olfaction came with the discoveries of the gene family coding for the olfactory receptor proteins (1) and the combinatorial mode of operation of these receptors (2). Odorous molecules enter the nose either from the front, by inhalation, or from the back, by diffusion from the mouth and respiratory tract. In the nose, they interact with an array of receptors. Each receptor type responds to a range of odorants, and each odorant stimulates a range of receptors. The signals thus generated are coded onto centers, known as glomeruli, in the olfactory bulb. The olfactory signals pass on upward through the brain and are interpreted finally, in the cortex, as odor. During the neurotransmission process, many interactions occur between olfactory signals and cortical feedback mechanisms, which include effects from other senses. Therefore, it is not surprising that simple structure/odor correlations are so elusive.
Origins of Life: Emergence of Amino Acids
Authors: Pascal Robert , Boiteau Laurent
Published: February 2008

Amino acids can be synthesized from inanimate matter through processes independent of living organisms. An overview of these processes occurring in various environments, including interstellar media, is given with a special emphasis on Strecker synthesis and related processes compatible with primitive Earth conditions. When analyzing their relevance to the origin of life, chemical pathways leading to α‐amino acids from activated precursors may be considered independent from further polymerization into peptides promoted by activating agents. Alternatively, both processes may also be connected to each other so that the emergence of amino acids and the prebiotic formation of peptide may have been closely associated. The last possibility is that prebiotic chemistries of amino acids and nucleotides may have been cooperating with each other in a way that led to the emergence of the genetic code and to a rudimentary translation apparatus.
Pentose Phosphate Pathway
Authors: Williams John F.
Published: February 2008

The elementary textbook treatment of the pentose phosphate pathway (PPP) describes its nature and occurrence in the cytoplasm of most cells. The reaction scheme is of two segments, oxidative and nonoxidative. The reactions of the oxidative segment are few and involve the decarboxylation of glucose 6‐phosphate (Glc 6‐P) to ribulose 5‐phosphate (Ru 5‐P) and CO2via 6‐phosphogluconolactone and 6‐phosphogluconate (6‐PG). Concomitant production of two moles of NADPH and H+for each mole of Glc 6‐P converted to Ru 5‐P. The nonoxidative reactions are depicted classically with an ordered reaction sequence of reversible steps for the interconversion of other pentose phosphate products that originate from Ru 5‐P by epimerase and isomerase enzymes. The reactions of the PPP also link the formation of sugar phosphate intermediates (glycolyl units) containing 3–7 carbon atoms that are generated by freely reversible equilibrium reactions catalyzed in fixed order by Transketolase and Tansaldolase. These reactions permit the following three biosynthetic PPP functions to emerge: cellular energetics, growth, and repair. Specifically via 1) the contribution by the oxidative segment of a high NADPH / NADP+redox potential that provideselectronsfor most reductive anabolic processes; 2) the formation of ribose 5‐phosphate (Rib 5‐P) for all nucleotide and nucleic acid biosynthesis, which is a demand that does not usually exceed 2% of all Glc metabolized by PPP activity; and (c) a storage pool of diverse phosphorylated glycolyl units that may be used directly or as signals for biosynthetic and energy‐yielding reactions by other pathways. Finally, selected reactions of the nonoxidative segment are also part of the most extensive synthetic and life‐sustaining event on the planet, namely the photosynthetic reductive path of CO2assimilation in all C‐3 plants.
Peptide Nucleic Acids (PNAs)
Authors: Achim Catalina , A. Armitage Bruce , H. Ly Danith , W. Schneider James
Published: February 2008

Peptide nucleic acid (PNA) is a chimeric molecule that consists of hydrogen‐bonding purine and pyrimidine heterocycles attached to a pseudopeptide backbone. The bases allow the recognition of specific DNA or RNA sequences, which results in hybrid multihelical structures. The lack of a negative charge on the PNA backbone eliminates Coulombic repulsion from target DNA and RNA strands, which results in high affinity hybridization. These properties have led to a diverse set of applications for PNA, which includes antisense/antigene inhibition of gene expression, various DNA/RNA detection assays, nucleic acid labeling and purification technologies, and programmed assembly of nanoscale materials. The modular design of PNA has led to the synthesis of several “next‐generation” analogs that promise to improve PNA's performance in many existing applications as well as to open doors to new applications. Although most prior research on PNA has focused on its nucleic acid‐like character, recent developments of the peptide‐like aspects of PNA promise to stimulate additionally the work on this fascinating DNA mimic.
Peptidomimetics
Authors: Toniolo Claudio , Formaggio Fernando
Published: February 2008

This review article provides an introduction to folded and extended conformational motifs of synthetic peptidomimetics as templates for chemical biology applications. Several variants of these 3‐dimensional structures have been assessed, which comprise versatile scaffolds for presentation of side‐chain and main‐chain peptide groups for molecular recognition. Specifically, relevant parameters and stereochemical consequences are discussed for helices of peptidomimetics based on: 1) α‐amino acids alkylated (e.g., methylated or ethylated) at the C
α
‐atom; 2) α,β‐didehydroamino acids, in particular α,β‐didehydrophenylalanine, with a carbon–carbon double bond between the α‐ and β‐positions; 3) N‐alkylated α‐amino acids, whereby the side chains typical of coded residues are transferred from the C
α
‐ to the N‐atom; 4) β‐amino acids, the subclass of residues investigated most extensively in which the amino and carboxyl functionalities are separated by more than one carbon atom; and 5) short‐range, backbone‐to‐backbone cyclizations that generate small‐ring, monolactam or dilactam building blocks.
Physical Chemistry in Biology
Authors: Cooper Alan
Published: February 2008

Physical chemistry is that area of science that attempts to describe the properties and processes of matter in terms of underlying physical laws. Biology is no exception to these laws. This introductory article briefly sketches the role played by traditional physical chemistry in analyzing and understanding the behavior and control of biologic processes, focusing mostly on the molecular level. Thermodynamics and kinetics place restrictions on the kinds of reactions and processes that can take place as well as on how fast they occur. Electrochemistry, a branch of thermodynamics that deals with charge transfer processes, underpins much of redox biochemistry and membrane phenomena. Spectroscopy gives rise to a wealth of experimental techniques for structural and functional analysis, while quantum chemistry lurks in the background.
Watson–Crick Base Pairs: Character and Recognition
Authors: Olson Wilma K. , Colasanti Andrew V. , Lu Xiang‐Jun , Zhurkin Victor B.
Published: February 2008

The unique Watson–Crick arrangement of hydrogen‐bonded bases in DNA accommodates two different, complementary purine–pyrimidine pairs, A·T = T·A and G·C = C·G, in a common spatial setting. Nature takes advantage of these isomorphous structures, which store genetic information in terms of the proton donor and acceptor atoms that hold the bases in place. As outlined here, the Watson–Crick base pairs carry other chemical signals that are used to recognize and to process specific sequences of bases. The relative stabilities of G·C versus A·T pairs reflect their different electronic structures. The distributions of electronic charge on the exposed major‐groove and minor‐groove edges of the base pairs present unique motifs for direct sequence recognition, and the deformations of the paired bases from ideal, planar configurations provide subtle, indirect recognition elements. The biologic significance of the latter signals is not fully understood but is becoming clearer as more and more high‐resolution structures of DNA and RNA are determined.
Polyketide Biosynthesis: Modular Polyketide Synthases
Authors: Buchholz Tonia J. , Kittendorf Jeffrey D. , Sherman David H.
Published: February 2008

Polyketides constitute a large class of microbial and plant‐derived secondary metabolites that displays a vast array of structural diversity. These organic molecules vary in molecular weight, functional group modification, and include linear, polycyclic, and macrocyclic structural forms. Currently, polyketide natural products find clinical use as antibiotics, antiparasitic agents, antifungals, anticancer drugs, and immunosuppressants. Given these impressive and wide‐ranging pharmacologic activities, an ever‐increasing demand is placed on natural products research to uncover novel polyketide metabolites for the benefit of human and animal health. Modular polyketide synthases are nature's platform for the expansion of chemical diversity. This review provides new perspectives on important biosynthetic mechanisms that contribute to this variety. This includes control of double‐bond configuration and regiochemistry, introduction of β‐branching during polyketide chain assembly, and other processes that contribute to introduction of unique chemical functionality into these fascinating systems.
DNAPolymorphisms: Tools for Detection
Authors: Sauer Sascha
Published: February 2008

DNA polymorphisms, such as single nucleotide polymorphisms (SNPs) and short tandem repeats (STRs), are used as genetic markers in linkage and association studies to dissect monogenic and polygenic traits. Structural variation and DNA methylation are additional sources of genetic variation and are becoming increasingly important, particularly in the analysis of cancer. In this article, biologic background, basic chemistries, and currently used technologies for the detection of these polymorphisms are presented with a focus on SNP analysis.
Programmed Cell Death as a Therapeutic Approach
Authors: Deshayes Kurt
Published: February 2008

Although turnover rate varies greatly with cell type, the survival of multicellular organisms requires the constant renewal of healthy cells and the removal of pathogen‐infected or damaged cells. A critical component of homeostasis is the proper regulation of programmed cell death or apoptosis. Both oversensitivity of crucial cells and resistance of malfunctioning cells to apoptotic stimuli threaten survival. A lack of death response permits mutant cells to survive normal death stimuli and potentially proliferate. Conversely, excess apoptosis removes cells required for organism survival. Restoring homeostasis by controlling apoptosis is a potentially powerful technique for alleviating disease.
Chemical Molecules that Regulate Transcription and Facilitate Cell‐to‐Cell Communication
Authors: Wuster Arthur , Babu M. Madan
Published: February 2008

In this article we review cell‐to‐cell communication in three groups of organisms: bacteria, fungi, and the amoeba
Dictyostelium
. In particular, we concentrate on cell‐density‐dependent quorum sensing, which seems to have evolved independently on several occasions. The biologic and chemical properties of select systems are outlined, and the way they affect transcription, often via cross‐genome interactions, is described for each of the three groups. Furthermore, we give a short overview of the methods that can be used to study quorum sensing. We also outline the general properties of quorum sensing systems, such as positive feedback and its link to starvation‐dependent pathways.
Ras Oncoproteins
Authors: Chenette Emily J. , Der Channing J.
Published: February 2008

The Ras small GTPase is well known for its role in regulating normal cellular proliferation, as well as in promoting human oncogenesis when activated mutationally. In signal transduction, Ras functions as a guanine nucleotide‐regulatedON–OFFswitch. Positioned at cellular membranes, Ras relays signals initiated by diverse extracellular stimuli to a complex network of cytoplasmic signaling cascades to affect changes in gene transcription, cell‐cycle progression, survival, and differentiation. The intense research into the biologic and chemical nature of Ras has prompted the development of a variety of biologic, pharmacologic, and genetic tools to study Ras signaling. Also, Ras is the founding member of a superfamily of Ras‐related and Ras‐like proteins. The technical approaches and chemical concepts that have been generated from the study of Ras have aided greatly the studies of Ras superfamily proteins, which revealed the versatile and divergent biologic roles of small GTPases in cell physiology.
Nucleobase Self‐Assembly Codes: Constitutional Transcription
Authors: Barboiu Mihail
Published: February 2008

The functional self‐organization can be transcribed readily into hybrid nanostructures by using the sol‐gel process. Accordingly, we have reported synthetic routes for preparing self‐organized systems that have been “frozen” in a siloxane matrix, as a straightforward approach to design a novel class of solid hybrid nanomaterials. Nucleobases oligomerization can be an advantageous choice to reinforce the controlled communication between interconnected “dynamic supramolecular” and “fixing siloxane” systems. Moreover, the different interconverting outputs that nucleobases may form by oligomerization define a dynamic polyfunctional diversity that may be “extracted selectively” by sol‐gel polymerization in solid state under the intrinsic stability of the different nucleobase‐pairing and G‐quadruplex‐based systems. The nucleobase‐type hybrid materials presented in this review unlock the door to the new self‐organized materials world paralleling that of biology.
Steroid Hormones
Authors: Simons S. Stoney
Published: February 2008

Five categories of steroid hormones exist in humans, including androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins. These hormones affect virtually every tissue and organ in the human body and play major roles in the development, differentiation, and homeostasis of normal individuals. Antisteroids usually possess nonsteroidal structures but still block the actions of the steroid hormones and are important tools in endocrine therapies of pathologic conditions. Therefore, how the body regulates where, when, and how much a response to steroids occurs is of major importance. Here we survey what is known about the genomic responses to steroid hormones, each of which is mediated by a unique intracellular receptor protein that interacts with the cellular DNA to modify the rates of gene transcription. These receptors are members of a much larger superfamily of steroid/nuclear receptors, most of which bind either nonsteroidal ligands or no known ligand. Nongenomic (i.e., pathways without initial involvement of genomic DNA) and secondary responses (i.e., changes that require protein synthesis to alter gene transcription) are additional important effects of steroid hormones but are not discussed here. The emphasis is on the biochemistry of the five classes of steroid hormones, the techniques used to study steroid hormone action, and the basic mechanistic steps by which steroids alter gene expression.
Synthetic Sphingolipids as Bioactive Molecules
Authors: Bittman Robert
Published: February 2008

Sphingolipids are a highly diverse class of lipids, which encompasses thousands of different structural combinations of the polar head group, amino group or amide chain, and sphingoid long‐chain base. Initially regarded as inert structural components of eukaryotic cell membranes and plasma lipoproteins, sphingolipids now are recognized as key participants in the life of virtually all cell types. They influence a myriad of biological processes, including cell growth, cell death, and susceptibility to inflammation and infections. The number of known sphingolipid‐dependent cell signaling systems is increasing rapidly as research efforts in this field progress. Sphingolipids stabilize transient microdomains in membranes known as “rafts.” Signaling proteins and receptors partition into membrane rafts, and some toxins, pathogens, and viruses bind to sphingolipids that are concentrated in rafts and subsequently undergo endocytosis (see also Lipid Signals: Extracellular). Synthetic, non‐natural analogs of sphingolipids hold promise as drug candidates for treatment of various disease states via their ability to perturb cell signaling, membrane trafficking, and binding of infectious agents. The repertoire of synthetic sphingolipids includes analogs that target enzymes in the sphingolipid biosynthetic pathway and those that act as antiproliferative agents, immunomodulators, and regulators of lipid raft formation (and resultant receptor function). This review is intended to bring attention to selected synthetic analogs of sphingosine, ceramide, and glycosphingolipids that may lead to therapeutic intervention in certain patho‐physiologic conditions.
Synthetic Peptides and Proteins to Elucidate Biological Function
Authors: Becker Christian F. W. , Goody Roger S.
Published: February 2008

The enormous progress made in the use of gene technological techniques over the past several decades has been the main driving force in the accumulation of our knowledge of biology at the molecular level. This progress has at times tended to push more classic approaches, such as those stemming from synthetic chemistry, into the background, and there has even been a tendency to regard contributions from this area as being superfluous. This attitude has begun to change recently, with the emergence of the field now referred to as chemical biology, and it is now appreciated that synthetic chemistry can make a unique contribution to the outstanding problems in fundamental biological and medically oriented research. The full potential of these methods is beginning to be realized in the area of peptide and protein synthesis, and this will be the topic of this article.
Systems Approach to Metabolism
Authors: Aoki‐Kinoshita Kiyoko F. , Kanehisa Minoru
Published: February 2008

The network structure of pathways can be studied from two complementary viewpoints; as networks of enzymes or as networks of chemical compounds. This structure enables more in‐depth analysis into metabolic pathways. From these networks, new features regarding pathways on both the local and the global levels can be detected. On the one hand, global features such as the scale‐free property of pathways have attracted much attention from the bioinformatics community. On the other hand, local features of networks such as pathway modules can retrieve and characterize subnetworks of related genes that are potentially involved in a particular function of the metabolic pathway. Systems analysis of metabolic pathways must focus not only on existing pathways, but also on reconstructing pathways for new genomes or filling in information regarding missing enzymes. By using the vast amounts of genomic data available, it is possible to reconstruct the metabolic maps of new genomes. Such genomic information has proved useful to refine prediction methods, and they can be complemented with chemical‐based information that is inherent in the same network. Overall, a systems approach to metabolism covers the realm of both the genomic and the chemical worlds in an integrated manner. We will show that the concepts of local network features in terms of both these worlds produce modules that can be integrated such that the global view of metabolism can be grasped. The current findings will be described systematically while also involving manual curation such that biologically accurate systems can be produced for analysis.