bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel reagents and reactions for drug design
Authors: Baker T. J. , Rew Y. , Goodman M. 
Published: October 2007

Abstract
In this presentation, we cover new results from two of our synthetic endeavors: guanidinylation reagents and novel bridged opioids. In the first part, we describe the applications of the diurethane-triflylguanidines to prepare target bioactive structures including peptides, heterocyclic drugs, and aminoglycoside derivatives. The formation of novel guanidinoglycosides led to a family of effective binders to the RNA recognition element of the HIV-1 Rev protein. In the second part, the syntheses of sulfur and amine-bridged cyclic opioids is described. These analogs exhibit enhanced binding, both in vitro and in vivo. Specifically, H-Tyr-c[d-Vall-Gly-Phe-d/l-Alal]-OH (Vall and Alal denote the lanthionine amino acid ends linked by a monosulfide bridge) is potent and highly δ -receptor selective while Tyr-c[(Nγ CH3 )-d-A2 bu-Gly-Phe-NHCH2CH2 -] though nonselective is one of the most potent opioids prepared to date. These molecules are representative of our design of novel peptidomimetic opioids.
Tissue-specific peptide pools. Generation and function
Authors: Ivanov Vadim T. , Yatskin Oleg N. , Kalinina Olga A. , Philippova Marina M. , Karelin Andrei A. , Shemyakin-Ovchinnikov Elena Yu. Blishchenko 
Published: October 2007

Abstract
Systematic analysis of several tissue extracts for peptide components followed by bioactivity studies leads to formulation of the concept of "tissue-specific peptide pools". According to that concept the endogenous proteolysis of proteins with well-established functions, such as hemoglobin, actin, and cellular enzymes in tissues leads to formation of the sets (or pools) of bioactive peptides. The sets are tissue-specific on one hand and conservative in a given tissue at normal conditions on the other. The content and the composition of pool components are sensitive both to pathologies linked with alterations of tissue metabolism and to prolonged physiological changes. In vivo formation of fragments of functional proteins includes several consecutive proteolytic stages inside the cells and further release of bioactive compounds into the surrounding medium. The effects of pool components take place predominantly at tissue and cellular levels, their effects being related to stimulation or inhibition of cell growth, induction of cell differentiation, and death. The above-mentioned features lead to the proposal that the main in vivo function of components of tissue-specific peptides is maintenance of tissue homeostasis, i.e., the normal ratio of functional, dividing, differentiating, and dying cells of tissues. Components of tissue-specific peptide pools display several features distinguishing them from "classical" peptide hormones and neuromediators. Summarizing, a novel peptidergic regulatory system is considered.
Designer cyclopeptides for self-assembled tubular structures
Authors: Ranganathan Darshan , Lakshmi C. , Haridas V. , Gopikumar M. 
Published: October 2007

Abstract
A simple design strategy for a facile and direct entry into hydrogen-bonded peptide nanotubes is delineated with polymethylene-bridged cystine-based macrocycles. The key feature of the design is the placement of a pair of self-complementary hydrogen-bonding (NH–CO or NH–CO–NH) groups at almost opposite poles of the ring. A large variety of cyclobisamides and bisureas prepared in a single step by direct condensation of commercially available 1,ω-alkane dicarbonyl dichloride or diisocyanate with either cystine diOMe or its extended bispeptide were examined by X-ray crystallography and shown to possess an inherent property of self-assembling into hydrogen-bonded, open-ended, hollow tubular structures. The totally hydrophobic interior of the cyclobisamide tubes creates a micro environment capable of solubilizing highly lipophilic substances in water. The cyclic bisurea tubes are demonstrated to act as excellent receptors for selective binding to 1,ω-alkane dicarboxylates. The scope of the design is extended to the creation of tubular structures by stacking of rings through aromatic π-π interactions.
Use of inhibitors to study reactions catalyzed by enzymes requiring pyridoxal phosphate as coenzyme
Authors: Adams Benjamin , Axelsson B. Svante , Beresford Kenneth J. M. , Church Nicola J. , Spencer Philip A. , Whyte Sheena M. , Young Douglas W. 
Published: October 2007

AbstractThe stereochemistry of a variety of pyridoxal phosphate-mediated enzymic reactions has been studied using enzyme inhibitors that are stereospecifically labeled in the β-position with deuterium. A versatile synthesis has been developed to prepare a wide variety of stereospecifically labeled d- and l-amino acids and inhibitors. Investigation of the "turnover" of β-chloro-d-alanine and d- and l-serine-O-sulfate by d-amino acid aminotransferase and l-aspartate aminotransferase respectively has shown that reaction within the active site of the former enzyme occurs with retention of stereochemistry. Although l-aspartate aminotransferase is an enzyme of the α-family, when it was incubated with β-chloro-l-alanine in the presence of 2-mercaptoethanol, β-substitution occurred. This was shown to involve retention of stereochemistry, an outcome typical of reactions catalyzed by enzymes of the β-family that have little or no homology with enzymes of the α-family. Formation of the "Schnackerz intermediate" has been studied as has the d-amino acid oxidase catalyzed reaction of the naturally occurring inhibitor d-propargylglycine.
Biological monitoring for exposure to volatile organic compounds (VOCs) (IUPAC Recommendations 2000)
Authors: Heinrich-Ramm R. , Jakubowski M. , Heinzow B. , Christensen J. Molin , Olsen E. , Hertel O. 
Published: October 2007

Abstract
This paper deals with the appropriate application of biological monitoring (BM) for exposure to volatile organic compounds (VOCs). Sampling guidelines, approved analytical procedures, quality control systems, detailed aspects for the interpretation of biomonitoring data, a compilation of international biological action values for VOC exposure at the workplace (e.g., BAT, BEI®), and state of the art reference values are outlined or referred to in this review for recommendation as guidelines for health professionals in occupational and environmental settings.
VOCs are frequently encountered at the workplace, in daily routines and widely used consumer products. They cover a broad spectrum of chemical classes with different physicochemical and biological properties. Inhalation is a prominent route of exposure due to their volatility but many VOCs can quite readily be absorbed through the skin. BM allows assessment of the integrated exposure by different routes including inhalation and concomitant dermal and oral uptake—a helpful tool for relating exposure to body burden and possible health effects. Because of the different toxicological profiles of VOCs, no uniform approach for BM can be recommended. VOCs in blood and urinary VOC metabolites are most often applied for BM. Limit values for workplace exposure have been established for many VOCs. In this field, profound analytical methodology and extensive experience exist in numerous international scientific laboratories for reliable routine application. Contamination and loss of VOCs during specimen collection, storage and sample treatment, and applied calibration procedure are the most important uncertainties for analytical quantification of VOCs in blood. For interpretation of the analytical results appropriate time of sampling, according to toxicokinetics of the compound, is crucial due to VOC elimination with short but differing biological half-lives. Lifestyle factors (such as smoking habits, alcohol consumption, and dietary habits), workload, personal working habits, exposure to VOC mixtures and endogeous factors (as genetic polymorphism for VOC metabolizing enzymes, body mass) contribute to BM results and have to be considered in detail. Future analytical work should focus on the improvement of analytical methodology of VOC determination in body fluids at low-level environmental exposure and evaluation of corresponding reference intervals.
p53 mutations as fingerprints of environmental carcinogens
Authors: Cetin-Atalay Rengul , Ozturk Mehmet 
Published: October 2007

Abstract
Mutations of the p53 tumor suppressor gene occur in a great majority of human cancers. The protein product of p53 gene is involved in DNA damage response. Consequently, p53 gene may be a preferred target for environmental carcinogens, which also act as DNA-damaging agents. This is probably why p53 mutations are frequent in cancers linked to environmental carcinogens. Moreover, these carcinogens leave molecular fingerprints on the p53 gene. Thus, the study of p53 mutation spectra has been a useful approach to implicate suspected carcinogens to different human cancers. This review provides further insight into the significance of p53 mutation spectra in ten common human malignancies (skin, liver, lung, bladder, breast, head and neck, esophagus, stomach and colorectal cancers, and hematological malignancies), in relation with environmental carcinogens.
Recent advances in metal carcinogenicity
Authors: Hartwig A. 
Published: October 2007

Abstract
The carcinogenicity of nickel, chromium, arsenic, cobalt, and cadmium compounds has long been recognized. Nevertheless, the mechanisms involved in tumor formation are not well understood. The carcinogenic potential depends on metal species; major determinants are oxidation state and solubility. Two modes of action seem to be predominant: the induction of oxidative DNA damage and the interaction with DNA repair processes, leading to an enhancement of genotoxicity in combination with a variety of DNA-damaging agents. Nucleotide excision repair (NER) is inhibited at low, non-cytotoxic concentrations of nickel(II), cadmium(II), cobalt(II), and arsenic(III); the repair of oxidative DNA base modifications is disturbed by nickel(II) and cadmium(II). One reason for repair inhibition appears to be the displacement of zinc(II) and magnesium(II). Potentially sensitive targets are so-called zinc finger structures present in several DNA repair enzymes such as the mammalian XPA protein and the bacterial formamidopyrimidine-DNA glycosylase (Fpg protein); detailed studies revealed that each zinc finger protein exerts unique sensitivities toward toxic metal ions. Taken together, toxic metal ions may lower the genetic stability by inducing oxidative DNA damage and by decreasing the repair capacity towards DNA lesions induced by endogenous and exogenous mutagens, which may in turn increase the risk of tumor formation.
A review of human and sub-human primate toxicity of hexachlorobenzene
Authors: Jarrell John , Gocmen Ayhan 
Published: October 2007

Abstract
The inadvertent exposure of a large cohort of individuals to hexachlorobenzene (HCB) in the mid-1950s in southeastern Turkey remains an environmental disaster that continues to fascinate and provide interesting observations concerning this ubiquitous chemical. A brief history of the exposure is presented with particular reference to the initial presentation of Pembe Yara and Porphyria Cutanea Tarda and later to reproductive performance in humans and sub-human primates. Differential toxicity is present in the oocytes of monkeys, with more severe damage identified in primordial germ cells rather than in growing oocytes. However, this observation did not express itself in women, as there was no increased incidence of premature menopause among those exposed. Germ cell toxicity remains a possible outcome of exposure, however. The serum HCB levels measured in exposed individuals predicted the lifetime risk of spontaneous abortion, not only in exposed individuals but also in the control populations, indicating that a possible population effect is present.
Use of genetically altered animal models in understanding the role of metallothionein in cadmium toxicity
Authors: Klaassen Curtis D. , Choudhuri Supratim 
Published: October 2007

Abstract
Acute Cd exposure produces liver injury, whereas chronic Cd exposure damages the kidney but not the liver. Previous experiments suggest that the low-molecular-weight, metal-binding protein metallothionein (MT) in liver protects against liver injury, but is responsible for the kidney injury observed after chronic Cd exposure. Thus, prior to the development of MT-transgenic and MT-knockout mice models, MT's role was always assumed to be a toxicological paradox, hepatoprotection but nephrotoxicity. The development of MT-transgenic and MT-knockout mice models has reconfirmed MT's protective role against Cd-induced hepatotoxicity, but it has challenged MT's suggested role in Cd-induced nephrotoxicity. In this communication, recent data using these genetically altered mice models indicate that MT protects against not only the Cd-induced hepatotoxicity, but also nephrotoxicity, hematotoxicity, immunotoxicity, and bone damage.
Environmental specimen banking. Herring gull eggs and breams as bioindicators for monitoring longterm and spatial trends of chlorinated hydrocarbons
Authors: Marth P. , Martens D. , Schramm K.-W. , Schmitzer J. , Oxynos K. , Kettrup A. 
Published: October 2007

Abstract
The German Environmental Specimen Bank (GESB) has been an important tool in contaminant monitoring and ecotoxicological research for more than one decade. The annual monitoring program provides a long-term database to determine trends in contaminant burdens in biota samples. Results of ten years of experience in the determination of chlorinated hydrocarbons (CHCs) in herring gull eggs collected in the North Sea and the Baltic Sea are presented. In addition, the study reports CHC concentrations in bream livers from the River Elbe between 1993-1997. Most of the compounds studied show a significant decline over time, especially in samples from East Germany. For specimens taken in West Germany, only small decreases or no changes of CHC levels were observed.
Role of catecholamines and cyclic AMP systems in phencyclidine and morphine dependence. Study of mutant mice
Authors: Nabeshima Toshitaka , Mamiya Takayoshi , Noda Yukihiro 
Published: October 2007

Abstract
To investigate an involvement of catecholamines and/or the cyclic adenosine monophosphate (cAMP) systems in the development of drug dependence, we examined whether phencyclidine (PCP) and morphine dependence were developed in tyrosine hydroxylase (TH) heterozygous (TH+/-) and cAMP response element binding protein (CREB) binding protein (CBP) heterozygous (CBP+/-) mice. PCP (8 mg/kg) induced place preference in wild-type mice pretreated with PCP (10 mg/kg/day for 28 days) and increased the level of cAMP in the striatum, but not in the thalamus/hypothalamus. In TH+/- and CBP+/- mice, however, we could not find PCP-induced place preference. The increased level of cAMP in the striatum was observed in CBP+/-, but not TH+/- mice. When wild-type mice pretreated with morphine (10 mg/kg) twice a day for 5 days were challenged with naloxone (5 mg/kg), they showed increased jumping, rearing, and forepaw tremor counts as a sign of withdrawal and an increased level of cAMP in the thalamus/hypothalamus, but not in the striatum. In TH+/- and CBP+/- mice, however, jumping and forepaw tremor counts were decreased compared to in wild-type mice. An increase in the level of cAMP in the thalamus/hypothalamus in CBP+/-, but not in TH+/- mice was observed. These results suggest that catecholamines and CBP are involved in the development of PCP and morphine dependence, and that changes in catecholaminergic and/or cAMP systems induced by repeated PCP and morphine treatments play an important role in the addiction to PCP and morphine.
The mechanism of the releasing action of amphetamine. Uptake, superfusion, and electrophysiological studies on transporter-transfected cells
Authors: Pifl C. , Sitte H. H , Reither H. , Singer E. A. 
Published: October 2007

Abstract
Amphetamine analogues are able to induce signs of neurotoxicity in the brain. In order to understand this type of neurotoxicity, the interaction of amphetamine with its molecular targets must be elucidated. These molecular targets are plasmalemmal and vesicular monoamine transporters. We investigated the interaction of amphetamine with these transporters in cells transfected with the respective cDNA. Superfusion and whole-cell, patch-clamp experiments were performed, and the toxicity of substrates of the transporters was studied. Amphetamine was taken up by dopamine transporter-expressing cells in a sodium-dependent and cocaine-blockable manner. Furthermore, it elicited inward currents in these cells concentration-dependently. Correlation of uptake, release, and patch-clamp experiments suggest that ion fluxes induced by substrate-gating on transporters may significantly contribute to the releasing action of amphetamine and of other transporter substrates. Dopamine accumulation into serotoninergic terminals depleted of serotonin by 3,4-methylenedioxymethamphetamine was discussed as a mechanism of Ecstasy-toxicity. This is in agreement with a toxic effect of intracellular dopamine which could be demonstrated on our transporter-overexpressing cells. These results, apart from their relevance for the toxicity by amphetamine analogues, may also have bearings on the mechanisms in neurodegenerative diseases affecting monoamine transmitters.
Atom efficiency and catalysis in organic synthesis
Authors: Sheldon Roger A. 
Published: October 2007

Abstract
The key to waste minimization in fine chemicals manufacture is the widespread substitution of classical organic syntheses employing stoichiometric amounts of inorganic reagents with cleaner, catalytic alternatives. The E factors (by waste per kg product) of chemical processes increase dramatically on going downstream from bulk to fine chemicals and pharmaceuticals, mainly owing to the use of "stoichiometric" methods. The concept of atom efficiency is a useful tool for rapid evaluation of the amount of waste generated by alternative processes. The general theme of atom-efficient, catalytic processes is illustrated with industrially relevant examples. These include catalysis by solid acids and bases, catalytic reductions and oxidations, catalytic C_C bond formation, asymmetric catalysis, biocatalysis, and catalysis in novel media (aqueous and fluorous biphasic systems, supercritical fluids, and ionic liquids).
Use of the life-cycle assessment (LCA) toolbox for an environmental evaluation of production processes
Authors: Herrchen Monika , Klein Werner 
Published: October 2007

Abstract
Green chemistry not only emphasizes the central production process of the "green" chemical, but it ultimately requires a life-cycle conceptual approach for each chemical product. A life-cycle conceptual approach comprises the consideration of all stages along the life cycle of a chemical (i.e., raw material extraction, pre-production, production, use, recycling, and disposal) as well as the consideration of environmental impacts caused by by-products and auxiliaries (such as solvents and additives, but also technical facilities which have to be provided to produce the green chemical). A significant improvement in the evaluation of green chemical products can be approached by the complementary use of the methodologies of life-cycle assessment (LCA) and risk assessment. The use and combination of both methodologies can be performed by a separate use of the instruments (depending on the scope, definition, and application of LCA), an iterative use of LCA and risk assessment, or a complete integration of both instruments. Pros and cons of these approaches are discussed.
Fats and oils as oleochemical raw materials
Authors: Hill Karlheinz 
Published: October 2007

Abstract
Vegetable oils and fats are important constituents of human and animal foodstuffs. Certain grades are industrially used and, together with carbohydrates and proteins, are important renewable resources compared to fossil and mineral raw materials, whose occurrence is finite. In concepts for new products, the price, performance, and product safety criteria are equally important and have a correspondingly high importance right at the start of product development. To ensure a high degree of product safety for consumers and the environment, renewable resources have often been shown to have advantages when compared with petrochemical raw materials and can therefore be regarded as being the ideal raw material basis. Results from oleochemistry show that the use of vegetable fats and oils allows the development of competitive, powerful products, which are both consumer-friendly and environment-friendly. Recently developed products, which fit this requirement profile, are the anionic surfactants cocomonoglyceride sulfate and the nonionic sugar surfactant alkyl polyglycoside. These products are used especially as mild surfactants in cosmetic formulations. In polymer applications derivatives of oils and fats, such as epoxides, polyols, and dimerizations products based on unsaturated fatty acids, are used as plastic additives or components for composites or polymers like polyamides and polyurethanes. In the lubricant sector fatty acid-based esters have proven to be powerful alternatives to conventional mineral oil products.
Utilization of TiO2 photocatalysts in green chemistry
Authors: Anpo Masakazu 
Published: October 2007

Abstract
Environmental pollution and destruction on a global scale have drawn attention to the vital need for totally new environmentally friendly, clean chemical technologies and processes, the most important challenge facing chemical scientists in the field of green chemistry. Strong contenders as environmentally harmonious catalysts are photocatalysts that operate at room temperature and in a clean manner, while applications of such safe photocatalytic systems are urgently desired for the purification of polluted water, the decomposition of offensive atmospheric odors as well as toxins, the fixation of CO2, and the decomposition of NOx and chlorofluorocarbons on a huge global scale. To address such enormous tasks, photocatalytic systems that are able to operate effectively and efficiently not only under UV light but also under the most environmentally ideal energy source, sunlight, must be established. To this end, we are moving in a positive direction with various practical applications already at hand, as is described.
The present report involves 1) new approaches in the design and development of second-generation titanium oxide photocatalysts which can operate effectively under visible light and/or solar beam irradiation, 2) practical industrial applications of titanium oxide photocatalysts in Japan, and 3) recent advances in green chemistry in Japan.
Oxidation reactions in the synthesis of fine and intermediate chemicals using environmentally benign oxidants and the right reactor system
Authors: Hoelderich Wolfgang F. , Kollmer Felix 
Published: October 2007

Abstract
This review outlines several approaches for designing new and environmentally friendly heterogeneously catalyzed oxidation processes for the synthesis of fine and intermediate chemicals. Environmentally benign oxidants such as molecular oxygen, hydrogen peroxide or nitrous oxide can be activated on suitable heterogeneous catalysts showing high activity and selectivity toward the desired oxygenated products. Several examples illustrate that features known from the synthesis of bulk chemicals can successfully be applied for manufacturing intermediate and specialty chemicals applying conventional industrial reactor systems. Direct oxidation of isoprenol, b-picoline, and benzene are chosen as examples for continuous gas-phase processes, oxidation of pinene and propylene as examples for semi-continuous or batchwise processes in the liquid phase.