bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptidomimetics for Receptor Ligands—Discovery, Development, and Medical Perspectives
Authors: Giannis Athanassios , Kolter Thomas 
Published: December 2003

AbstractPeptides, as neurotransmitters, neuromodulators, and hormones, influence a multitude of physiological processes by signal transduction mediated through receptors. In addition, during the last 20 years their role in the appearance or maintenance of various diseases could be unequivocally proven. Agents that can imitate or block the biological functions of bioactive peptides (agonists or antagonists, respectively) can be considered as aids for the investigation of peptidergic systems and also as therapeutic agents. The suitability of bioactive peptides as therapeutic agents was examined after preliminary pharmacological experiments. It was thereby shown that based on their pharmacological properties, for example degradation by peptidases or poor bioavailability, they could be employed as drugs in only a few cases. To solve this problem peptidomimetics, compounds that act as substitutes for peptides in their interaction with receptors, have been synthesized. In comparison with native peptides they show higher metabolic stability, better bioavailability, and longer duration of action. Peptidomimetics with antagonistic properties were also developed within the range of these investigations. As a result, new types of treatment and therapy for a series of diseases are possible. Although peptidomimetics have been developed largely by empirical methods (e.g. modification of native peptides, optimization of lead structures), methods for rational design based on investigations into the structure of peptidepeptide receptor complexes and studies of conformation energies, among others, are gradually being established.
Ultramicroelectrodes in Electrochemistry
Authors: Heinze Jürgen 
Published: December 2003

AbstractIn the 1950s and 1960s fundamental developments in electrochemical methods included voltammetry and low signal techniques. A generation later, the discovery of the unusual properties of ultramicroelectrodes has opened new possibilities of analyzing electrode processes. The changes in mass transport conditions bring about extremely high current densities at ultramicroelectrodes, whereas the currents themselves become very small. This little‐noticed phenomenon allows for many electroanalytical applications that are not possible with conventional electrodes, especially experiments in solutions with very low electrolyte concentrations, in nonpolar solvents, in solids, and even in gases. In addition, two factors— changes in the experimental time scale at low scan rates because of the size of the electrode, and insignificant iR effects at very high scan rates—make it possible to study very fast homogeneous and heterogeneous electrode processes.
Organoelement Compounds with AlAl, GaGa, and InIn Bonds
Authors: Uhl Werner 
Published: December 2003

AbstractIn the attempt to synthesize compounds with aluminum in a low oxidation state and an AlAl bond, by the reduction of alkylaluminum halides with alkali metals, analogous to a Wurtz coupling, in general the deposition of elemental aluminum and the formation of the corresponding trialkylaluminum compounds is observed. Thus, tetrasubstituted dialuminum compounds R2AlAlR2, apart from a few poorly characterized examples, were for a long time considered part of an unverified class of substances. Only with the sterically very highly shielded tetrakis[bis(trimethylsilyl)methyl]dialuminum did we achieve the synthesis of the first completely characterized organoelement compound with unlimited stability, which shows aluminum in the oxidation state + II and has an AlAl bond. In the meantime, corresponding compounds for the elements gallium and indium have been obtained. With the simple access to tetrasubstituted dimetal compounds, a fascinating new research area has opened for preparative chemistry, in which the particular interest will naturally lie in the reactive properties of the metal‐metal bond.
Bacteria and the Biodegradation of Chemicals Achieved Naturally, by Combination, or by Construction
Authors: Gottschalk Gerhard , Knackmuss Hans‐Joachim 
Published: December 2003

AbstractThe natural potential of bacteria for the biological degradation of synthetic compounds is greater than is commonly supposed and extends to many heteroarenes and even some chloroarenes. An increase in the number of substituents on the aromatic ring or a certain substitution pattern is what confers xenobiotic character to a compound. In addition, when enzymes with low substrate specificity encounter foreign compounds with random variations, products with very strong xenobiotic character often result. In this case, changing the conditions or introducing a cooperation between several different types of bacteria can be used to degrade these compounds. Finally, mineralization, the complete breakdown of organic substances into carbon dioxide and inorganic salts, of xenobiotics previously regarded as persistent can be achieved by taking advantage of natural or induced gene transfer to construct hybrid degradative pathways. After an introduction to the world of bacteria and their place in Nature, we will describe their natural potential for biodegradation with reference to aliphatic and aromatic hydrocarbons. The discussion will then turn to the types of the substituents that confer xenobiotic properties to compounds and how these compounds are degraded despite their xenobiotic character.
Structures of Organo Alkali Metal Complexes and Related Compounds
Authors: Weiss Erwin 
Published: December 2003

AbstractThe investigation of the reactivity and structure of organometallic compounds of alkali metals has experienced a blustering development in the last decades. This class includes compounds that are especially important for our understanding of chemical bonding and also quite simple, for example methyl alkali metal complexes, whose structures have been unequivocally determined. Organometallic compounds of alkali metals (and also magnesium) generally exist as ion aggregates whose properties can be significantly modified through solvation by, for example, ether or amines. Important advances in the synthesis of new compounds, especially those of the heavier alkali metals, have been based on these results. It was long believed that the alkali metals had little tendency to undergo coordination and that their coordination chemistry would offer few surprises. This picture has now changed completely. Results from crystal structure investigations have revealed a variety of often surprising structure types (rings, heterocubanes, chains, layers, etc.) not only with the organometallic compounds but also with the amides, imides, alkoxides, phenoxides, enolates, and even halides. A comparison reveals interesting similarities between compounds that appear to be so different and leads to a general classification of the structure types possible with C, N, O, and halo ligands.
Hydrophobic Effects. Opinions and Facts
Authors: Blokzijl Wilfried , Engberts Jan B. F. N. 
Published: December 2003

AbstractThe term hydrophobic interactions denotes the tendency of relatively apolar molecules to stick together in aqueous solution. These interactions are of importance in many chemical disciplines, including the chemistry of in vivo processes. Enzyme‐substrate interactions, the assembly of lipids in biomembranes, surfactant aggregation, and kinetic solvent effects in water‐rich solutions are all predominantly governed by hydrophobic interactions. Despite extensive research efforts, the hydration of apolar molecules and the noncovalent interactions between these molecules in water are still poorly understood. In fact, the question as to what the driving force for hydrophobic intractions is shifts the study into a quest for a detailed understanding of the remarkable properties of liquid water. This review highlights some of the novel insights that have been obtained in the past decade. The emphasis is on both hydrophobic hydration and hydrophobic interactions since both phenomena are intimately connected. Several traditional views have been found to be deeply unsatisfactory, and courageous attempts have been made to conceptualize the driving force behind pairwise and bulk hydrophobic interactions. The review presents an admittedly personal selection of the recent experimental and theoretical developments, and when necessary, reference is made to relevant studies of earlier date.
The Unique Antithrombin III Binding Domain of Heparin: A Lead to New Synthetic Antithrombotics
Authors: van Boeckel Constant A. A. , Petitou Maurice 
Published: December 2003

AbstractHeparin, a sulfated glycosaminoglycan, is well known for its anticoagulant effect mediated by the serine protease inhibitor antithrombin III (AT III). Heparin has been used clinically for more than half a century for the prophylaxis and treatment of venous thrombosis and thromboembolism. Up until the 1980s it was assumed that the biological activity of heparin was mainly caused by its polyanionic character. However, this paradigm was contradicted when it was discovered that part of the heparin polysaccharides contains a well‐defined pentasaccharide domain that specifically binds and activates AT III. The specificity of the interaction between the characteristic pentasaccharide and AT III has become more obvious after the synthesis and biological testing of various heparin analogues. This article reviews the synthesis of the heparin pentasaccharide, some closely related counterparts, and some highly modified analogues. With the aid of molecular modeling and through “tailored” molecular modifications of the pentasaccharide, much knowledge has been gained concerning structure‐activity relationships. On this basis not only have more potent and simplified derivatives been developed, but also the recognition between heparin and AT III can now be understood in greater detail at the molecular level.
Luminescent Labels—More than Just an Alternative to Radioisotopes?
Authors: Mayer Andreas , Neuenhofer Stephan 
Published: December 2003

AbstractChemical, chromatographic, or spectrometric methods are generally unsuitable for the detection of molecules in the nano and subnanogram region because of their low sensitivity. The radioimmunoassay (RIA) developed by Yalow and Berson in 1959 combined the high sensitivity of radioactively labeled substances with the high specificity of immunological reactions for the first time. In this way it was possible to detect quantitatively the tiniest traces of substances in the presence of an excess of other, in some cases, similar foreign substances without prior enrichment. Immunoassays have certainly developed to become the most valuable analytical tool of in vitro diagnostics and are today routinely employed for the detection of endogenous and exogenous substances (e.g. hormones, tumor‐associated proteins, bacteria, viruses, toxins, drugs, etc). The many disadvantages of radioactivity such as the required handling licenses, disposal costs, precautions necessary to prevent risks to health, short shelf‐life, and limited sensitivity soon led to the search for other nonradioactive labeling methods. Encouraged by the development of light measuring techniques and the commercial availability of highly sensitive apparatus, radioactive isotopes as labels are today being replaced increasingly by enzymes, fluorophores, or luminophores. Some of the new luminescent labels have, however, not only facilitated replacement of radioisotopes, but also a breakthrough into what has until now been unattainable levels of sensitivity. The following article reviews the methods of luminescent labeling and their applications mainly in the area of immunoassays.
Are Polar Organometallic Compounds “Carbanions”? The Gegenion Effect on Structure and Energies of Alkali‐Metal Compounds
Authors: Lambert Christoph , von Ragué Schleyer Paul 
Published: December 2003

AbstractPolar organometallic compounds such as alkyllithium compounds or Grignard reagents often are conceived as “carbanions”, although it is well known from experiments that the metal gegenions may have a strong, and often directing, influence on the reactivity (for example, the basicity vs. the nucleophilicity) of the “carbanion”. This demonstrates that “carbanions” are tightly associated ion pairs, at least in commonly used less polar or nonpolar solvent systems like ethers or hydrocarbons. However, despite about ninety years of widespread application of these organometallic compounds as bases or nucleophilic reagents, the role of the gegenion is not yet understood fully. The focus of this review is on the inherent influences of the metal gegenion on the structures, reaction energies, and activation barriers of some representative alkali‐metal compounds. While most comparisons of physical and chemical properties determined experimentally for Group I compounds are precluded due to different substituents, solvents, ligands, etc., ab initio calculations of model compounds can yield intrinsic data that are useful for a better understanding of chemical behavior. For this reason, most of the data reviewed in this article are based on quantum chemical calculations, which are compared with experimental data where available.
Peptidyl‐Prolyl cis/trans Isomerases and Their Effectors
Authors: Fischer Gunter 
Published: December 2003

AbstractChanges in the conformation of the units within the peptide chain are the elementary processes in the folding of a protein into its native three‐dimensional structure. Even a few years ago protein folding in vivo was considered to be an autonomous process not requiring the help of enzymes or auxiliary substances. Recently an increasing number of proteins that assist in the folding process have been found; these include enzymes that catalyze conformational interconversions. The cis/trans isomerization of the petptide bond N‐terminal to a praline residue is catalyzed by peptidyl‐prolyl cis/trans isomerases (PPIases). Two families of these ubiquitous and phylogenetically highly conserved enzymes are known, the cyclophilins and FK506‐binding proteins. Their catalytic activity is extremely highmdash;the rate constants for the bimolecular reactions they catalyze approach the diffusion‐controlled limit for enzyme‐substrate reactions. These enzymes increase the rate of isomerization in oligopeptides as well as in intermediate in protein folding. It is not yet known which structural units in the cell serve as substrates and exactly which reactions are catalyzed. However, these isomerases have been shown to interact with the heat shock proteins of the nonactivated steroid receptors and with the gag polyprotein of the AIDS HIV‐1 virus. The immunosuppressive agents cyclosporine A and FK506 are highly effective inhibitors for PPIases. Surprisingly these compounds affect the signal cascade of T cells but not through enzyme inhibition; the inhibitor‐enzyme complexes themselves are the active agents. These complexes exhibit properties not displayed by the individual components and thus are able to affect other cellular components. The current model of the suppression of the antigen‐ and mitogen‐stimulated clonal expansion of T cells is presented here.
A Highly Distorted and an Undistorted Borirane, CBH Hyperconjugation Induced by CSiH Hyperconjugation
Authors: Balzereit Christian , Kybart Claudia , Winkler Heinz‐Jürgen , Massa Werner , Berndt Armin 
Published: December 2003

AbstractFor corrigendum see DOI:10.1002/anie.199416681
Use of protein charge ladders to study electrostatic interactions during protein ultrafiltration
Authors: Ebersold Mareia Frost , Zydney Andrew L. 
Published: December 2003

AbstractRecent studies have demonstrated the importance of electrostatic interactions in membrane systems, but there is still controversy about the underlying phenomena. Protein charge ladders, consisting of a set of chemical derivatives of a given protein that differ by single charge groups, were used to quantify the electrostatic interactions during protein ultrafiltration. Myoglobin charge ladders were generated by acylation, with the different derivatives analyzed simultaneously by capillary electrophoresis. Filtration experiments were performed using polyethersulfone and composite regenerated cellulose membranes, with the membrane charge determined from the streaming potential. As expected, the rejection increased as the protein became more heavily charged due to the increase in electrostatic repulsion. However, the transmission of the weakly charged myoglobin species increased dramatically at very low ionic strength. This increase in transmission was attributed to a shift in pH within the pore caused by hydrogen ion partitioning into the charged membrane. The sieving data were in good agreement with theoretical calculations accounting for the effects of this pH shift on the electrostatic interactions. © 2003 Wiley Periodicals, Inc.
Recolonization of laser‐ablated bacterial biofilm
Authors: Nandakumar Kanavillil , Obika Hideki , Utsumi Akihiro , Toshihiko Ooie , Yano Tetsuo 
Published: December 2003

AbstractThe recolonization of laser‐ablated bacterial monoculture biofilm was studied in the laboratory by using a flow‐cytometer system. The marine biofilm‐forming bacterium Pseudoalteromonas carrageenovora was used to develop biofilms on titanium coupons. Upon exposure to a low‐power pulsed irradiation from an Nd:YAG laser, the coupons with biofilm were significantly reduced both in terms of total viable count (TVC) and area cover. The energy density used for a pulse of 5 ns was 0.1 J/cm2 and the durations of irradiation exposure were 5 and 10 min. When placed in a flow of dilute ZoBell marine broth medium (10%) the laser‐destructed bacterial film in a flow‐cytometer showed significant recovery over a period of time. The flow of medium was regulated at 3.2 ml/min. The increase in area cover and TVC, however, was significantly less than that observed for nonirradiated control (t‐test, P< 0.05). The coupons were observed for biofilm area cover and TVC at different intervals (3, 6, and 9 h) after irradiation. While the biofilm in the control coupon at the end of 9 h of exposure showed 95.6 ± 4.1% cover, the 5‐ and 10‐min irradiated samples after 9 h showed 60.3 ± 6.5 and 37.4 ± 12.1% area cover, respectively. The reduced rate of recolonization compared to control was thought be due to the lethal and sublethal impacts of laser irradiation on bacteria. This observation thus provided data on the online recolonization speed of biofilm, which is important when considering pulsed laser irradiation as an ablating technique of biofilm formation and removal in natural systems. © 2003 Wiley Periodicals, Inc.
Strategies for the cryopreservation of microencapsulated cells
Authors: Heng Boon Chin , Yu Hanry , Ng Soon Chye 
Published: December 2003

AbstractThe major challenge in developing cryopreservation protocols for microencapsulated cells is that the relatively large size (300–400 μm) and the fragile semipermeable membrane of microcapsules makes them particularly prone to cryodamage. Rapid‐cooling cryopreservation protocols with high DMSO concentrations (3.5M, 25% v/v) resulted in low post‐thaw cell viability (<10%), which did not improve with higher concentrations (4.5M, 32% v/v) and longer exposure to DMSO, even though the majority of microcapsules (60–80%) remained intact. Subsequent investigations of slow cooling with a range of DMSO and EG concentrations resulted in a much higher post‐thaw cell viability (80–85%), with the majority of the microcapsules remaining intact (∼60%) when DMSO was used at a concentration of 2.8M (20% v/v) and EG at a concentration of 2.7M (15% v/v). The presence of 0.25M sucrose significantly improved post‐thaw cell viability upon slow cooling with 2.8M (20% v/v) DMSO, although it had no effect on microcapsule integrity. Multistep exposure and removal of sucrose did not significantly improve either post‐thaw cell viability or microcapsule integrity, compared to a single‐step protocol. Ficoll 20% (w/v) also did not significantly improve post‐thaw cell viability and microcapsule integrity. Hence, the optimal condition for microcapsule cryopreservation developed in this study is slow cooling with 2.8M (20% v/v) DMSO and 0.25M sucrose. © 2003 Wiley Periodicals, Inc.
Maximizing interferon‐γ production by chinese hamster ovary cells through temperature shift optimization: Experimental and modeling
Authors: Fox Stephen R. , Patel Upasana A. , Yap Miranda G. S. , Wang Daniel I. C. 
Published: December 2003

AbstractThe Chinese hamster ovary (CHO) cell line producing interferon‐γ (IFN‐γ) exhibits a 2‐fold increase in specific productivity when grown at 32°C compared to 37°C. Low temperature also causes growth arrest, meaning that the cell density is significantly lower at 32°C, nutrients are consumed at a slower rate and the batch culture can be run for a longer period of time prior to the onset of cell death. At the end of the batch, product concentration is doubled at the low temperature. However, the batch time is nearly doubled as well, and this causes volumetric productivity to only marginally improve by using low temperature. One approach to alleviate the problem of slow growth at low temperature is to utilize a biphasic process, wherein cells are cultured at 37°C for a period of time in order to obtain reasonably high cell density and then the temperature is shifted to 32°C to achieve high specific productivity. Using this approach, it is hypothesized that IFN‐γ volumetric productivity would be maximized. We developed and validated a model for predicting the optimal point in time at which to shift the culture temperature from 37°C to 32°C. It was found that by shifting the temperature after 3 days of growth, the IFN‐γ volumetric productivity is increased by 40% compared to growth and production at 32°C and by 90% compared to 37°C, without any decrease in total production relative to culturing at 32°C alone. The modeling framework presented here is applicable for optimizing controlled proliferation processes in general. © 2003 Wiley Periodicals, Inc.
Efficient production of a bioactive, multiple disulfide‐bonded protein using modified extracts of Escherichia coli
Authors: Kim Dong‐Myung , Swartz James R. 
Published: December 2003

AbstractIn this report, we demonstrate that a complex mammalian protein containing multiple disulfide bonds is successfully expressed in an E.coli‐based cell‐free protein synthesis system. Initially, disulfide‐reducing activities in the cell extract prevented the formation of disulfide bonds. However, a simple pretreatment of the cell extract with iodoacetamide abolished the reducing activity. This extract was still active for protein synthesis even under oxidizing conditions. The use of a glutathione redox buffer coupled with the DsbC disulfide isomerase and pH optimization produced 40 μg/mL of active urokinase protease in a simple batch reaction. This result not only demonstrates efficient production of complex proteins, it also emphasizes the control and flexibility offered by the cell‐free approach. © 2003 Wiley Periodicals, Inc.