bluuebunny/crossref_metadata_2025_split huggingface dataset:
Essential Fatty Acids: Physiology and Clinical Significance
Authors: Das Undurti N. 
Published: February 2008

AbstractEssential 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

Abstract

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

Abstract
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

Abstract
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

AbstractNAD(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

AbstractOceans 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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

AbstractNucleic 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

AbstractSmell 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

Abstract
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

AbstractThe 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

AbstractPeptide 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

Abstract

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

AbstractPhysical 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

AbstractThe 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

Abstract
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

AbstractDNA 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.