bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ab Initio Structure/Reactivity Investigations of Illudin‐Based Antitumor Agents: A Model for Reaction in vivo
Authors: Gregerson Laura N. , McMorris Trevor C. , Siegel Jay S. , Baldridge Kim K. 
Published: December 2003

Abstract(Hydroxymethyl)acylfulvene (HMAF, irofulven; 4), a third‐generation derivative of a natural product extracted from the mushroom Omphalotus illudens, is selectively toxic towards certain forms of malignant tumors. Conversion of HMAF and cognates to stable aromatic derivatives is triggered by thiol attack in vitro and in vivo. Quantum‐chemical methods predict well the structure for several functionalized derivatives of irofulven as compared to known X‐ray crystallographic structures. Computational reaction profiles for thiol attack and aromatic rearrangement of irofulven and illudin S, a toxin from which irofulven is derived, provide insight into HMAF's selectivity and toxicity. Methods used include hybrid density‐functional theory (HDFT), HartreeFock (HF), and MøllerPlesset second‐order perturbation theory (MP2). Solvent effects have been explored by means of the new continuum‐solvation method, COSab, presented in an accompanying paper.
Synthesis, CD Spectra, and Enzymatic Stability of β2‐Oligoazapeptides Prepared from (S)‐2‐Hydrazino Carboxylic Acids Carrying the Side Chains of Val, Ala, and Leu
Authors: Lelais Gérald , Seebach Dieter 
Published: December 2003

Abstractβ‐Peptides offer the unique possibility to incorporate additional heteroatoms into the peptidic backbone (Figs. 1 and 2). We report here the synthesis and spectroscopic investigations of β2‐peptide analogs consisting of (S)‐3‐aza‐β‐amino acids carrying the side chains of Val, Ala, and Leu. The hydrazino carboxylic acids were prepared by a known method: Boc amidation of the corresponding N‐benzyl‐L‐α‐amino acids with an oxaziridine (Scheme 1). Couplings and fragment coupling of the 3‐benzylaza‐β2‐amino acids and a corresponding tripeptide (N‐Boc/C‐OMe strategy) with common peptide‐coupling reagents in solution led to β2‐di, β2‐tri‐, and β2‐hexaazapeptide derivatives, which could be N‐debenzylated (4–9; Schemes 2–4). The new compounds were identified by optical rotation, and IR, 1H‐ and 13C‐NMR, and CD spectroscopy (Figs. 4 and 5) and high‐resolution mass spectrometry, and, in one case, by X‐ray crystallography (Fig. 3). In spite of extensive measurements under various conditions (temperatures, solvents), it was not possible to determine the secondary structure of the β2‐azapeptides by NMR spectroscopy (overlapping and broad signals, fast exchange between the two types of NH protons!). The CD spectra of the N‐Boc and C‐OMe terminally protected hexapeptide analog 9 in MeOH and in H2O (at different pH) might arise from a (P)‐314‐helical structure. The N‐Boc‐β2‐tri and N‐Boc‐β2‐hexaazapeptide esters, 7 and 9, were shown to be stable for 48 h against the following peptidases: pronase, proteinase K, chymotrypsin, trypsin, carboxypeptidase A, and 20S proteasome.
New Chromium Enolates
Authors: Kündig E. Peter , Bernardinelli Gérald , Kondratenko Mikhail , Robvieux Fabrice , Romanens Patrick 
Published: December 2003

AbstractThree new (η2‐acrylate)(η6‐arene)dicarbonylchromium complexes are reported. They were obtained either by CO/acrylate exchange in [Cr(η6‐benzene)(CO)3] (1) via the photolytically generated η2‐cyclooctene intermediate or by arene exchange in [Cr(η2‐methyl acrylate)(η6‐benzene)(CO)2] (3) (Scheme 1). On crystallization, [Cr(η2‐methyl acrylate)(η6‐o‐xylene)(CO)2] (5) underwent partial resolution. The degree of this resolution was analyzed via X‐ray crystal‐structure determination (Fig. 1) and was correlated to the CD spectra in solution (Fig. 6), thus allowing the assignment of the absolute configuration. The reaction of [Cr(η2‐acrylate)(η6‐benzene)(CO)2] complexes with cyclopentad‐1,3‐diene or 1H‐indene afforded new (η6‐cyclopenta‐2,4‐dien‐1‐yl)‐ or (η6‐1H‐inden‐1‐yl)(η3‐oxaallyl)chromium complexes (Scheme 2). A mechanism is proposed that involves arene‐ligand substitution by the diene ligand, initiated by haptotropic rearrangement of the acrylate from a η2‐ to a η4‐coordination mode, followed by hydride migration from the diene to the acrylate (Scheme 3). An X‐ray crystal‐structure determination of [Cr(CO)2(η5‐1H‐inden‐1‐yl){η3‐CH(CH2CF3)C(O)OEt}] (8) reveals a metal enolate that is best described as η3‐oxaallyl species (Fig. 2). A shorter, more‐efficient route to the [Cr(η5‐1H‐inden‐1‐yl)(η3‐oxaallyl)] complexes was devised via the reaction of [Cr(CO)2(η2‐cyclooctene)(η6‐1H‐indene)] with methyl acrylate (Scheme 4).
Stereochemical Course of the Formation of the C(7)‐Formyl Group from a Chiral Methyl Group during the Transformation of Chlorophyllide a into Chlorophyllide b
Authors: Shoolingin‐Jordan Peter M. , Williams Stephen C. 
Published: December 2003

AbstractThe biosynthesis of chlorophyll a and chlorophyll b from (2R,3R)‐ and (2S,3S)‐5‐amino[2,3‐14C2,2,3‐2H2,2,3‐3H2]levulinic acid in greening barley has established that chlorophyllide a oxidase catalyses the transformation of the methyl group at C(7) of chlorophyllide a into the CHO group of chlorophyllide b with the loss of HSi from the 7‐(hydroxymethyl)chlorophyllide intermediate.
Building [2]Catenanes around a Tris(diimine)ruthenium(2+) ([Ru(diimine)3]2+) Complex Core Used as Template
Authors: Mobian Pierre , Kern Jean‐Marc , Sauvage Jean‐Pierre 
Published: December 2003

AbstractIn the course of the last two decades, the use of transition metals as templates for constructing catenanes has almost exclusively been restricted to tetrahedral copper(I). The present work is dealing with an octahedral metal, ruthenium(II), coordinated to three bidentate chelates. Incorporation of two chelates (1,10‐phenanthroline) in a ring allows to prepare a C2‐symmetric ruthenium complex, the two chelates being disposed cis to one another (see 142+ and 162+ in Scheme 5 and 6, resp.). The ring is large enough to accomodate a third chelate, thus allowing the metal‐directed threading of a long fragment containing the third chelate (2,2′‐bipyridine derivative; see 232+ and 242+ in Scheme 8). The last step consists of a ring‐closing metathesis reaction with two terminal olefins. The two ruthenium(II)‐complexed catenanes 252+ and 262+ were prepared by using this strategy, each containing a 42‐membered ring interlocked to a larger macrocycle (50‐ or 63‐membered ring) incorporating the two 1,10‐phenanthroline chelates. It is expected that these catenanes can be set in motion under light‐irradiation, thus behaving as photochemically driven molecular machines.
On Penicillin‐Binding Protein 1b Affinity‐Labeling Reagents
Authors: Volke Daniela , Daghish Mohammed , Hennig Lothar , Findeisen Matthias , Giesa Sabine , Oehme Ramona , Welzel Peter 
Published: December 2003

AbstractThe synthesis of some 3‐aryl‐3‐(trifluoromethyl)3H‐diazirine and benzophenone‐based photoaffinity labels is reported. The photolabile group is bound to a scaffold that also accommodates functional groups to which an indicator unit (biotin) and the bioactive ligand can be attached orthogonally. To three of the labels, moenomycin was conjugated with the aim to provide tools for the identification of the moenomycin binding site within the transglycosylase domain of the enzyme PBP 1b. Some preliminary photoaffinity‐labeling experiments were carried out.
Derivatives of Coenzyme F430 with a Covalently Attached α‐Axial Ligand. Part I
Authors: Bauer Carsten , Jaun Bernhard 
Published: December 2003

AbstractX‐Ray structures of the enzyme methyl‐coenzyme M reductase show that the Ni‐center in the prosthetic group coenzyme F430 is penta‐ or hexacoordinated with the carboxamide group of a glutamine residue occupying the axial coordination site on the α‐side of the macrocycle. To obtain diastereoselectively coordinated complexes for mechanistic and spectroscopic studies of the free coenzyme in solution, we aimed to prepare partial‐synthetic derivatives of coenzyme F430 that have a coordinating group attached via a linker to one of the propanoic acid side chains. By using molecular‐mechanics calculations and two different conformational search methods, a set of 50 structures containing imidazole or pyridine units as potential ligands were computationally tested according to geometric criteria defining coordinating conformations. The best candidates proved to be proline‐containing tri‐ and tetrapeptides with a methyl‐histidine as the C‐terminal residue. These linkers were synthesized, and their conformation was determined by NMR. Refinement of the molecular modeling by using the experimentally determined geometric restraints allowed us to decide that the tripeptide Pro‐Pro‐His(π‐Me)‐OMe (10) was the most promising of all tested structures for attachment to the side chain at C(3) or C(13) of F430.
Derivatives of Coenzyme F430 with a Covalently Attached α‐Axial Ligand. Part II
Authors: Bauer Carsten , Jaun Bernhard 
Published: December 2003

AbstractCoenzyme F430 pentamethyl ester 2 was partially hydrolyzed to a mixture of the five F430 tetramethyl esters 7–11, which were separated by HPLC and identified by means of a full NMR characterization. The tetramethyl ester with a free COOH group at the side chain at C(3) of F430 was coupled to the N‐terminus of the peptidic spacerligand construct 12 selected and studied as described before. The UV/VIS and NMR spectra in CH2Cl2/3,3,3‐trifluoroethanol 6 : 1 show that the new derivative, the NiII(33‐dehydroxy‐83,122,133,182‐tetra‐O‐methyl‐F430‐33‐yl)‐L‐prolyl‐L‐prolyl‐Nπ‐methyl‐L‐histidine methyl ester (13), is an intramolecular, pentacoordinate, paramagnetic complex. In the same solvent system, the parent 33,83,122,133,182‐penta‐O‐methyl‐F430 (2) is four coordinate and diamagnetic even in the presence of equimolar 1H‐imidazole. Protonation of the axially coordinating histidine residue of 13 gave the diamagnetic tetracoordinate base‐off form, which allowed us to establish the constitution of 13 by NMR.
Pentopyranosyl Oligonucleotide Systems. 9th Communication
Authors: Pitsch Stefan , Wendeborn Sebastian , Krishnamurthy Ramanarayanan , Holzner Armin , Minton Mark , Bolli Martin , Miculca Christian , Windhab Norbert , Micura Ronald , Stanek Michael , Jaun Bernhard , Eschenmoser Albert 
Published: December 2003

AbstractPyranosyl‐RNA (‘p‐RNA’ ) is an oligonucleotide system isomeric to natural RNA and composed of the very same building blocks as RNA. Its generational, chemical, and informational properties are deemed to be those of an alternative nucleic acid system that could have been a candidate in Nature's evolutionary choice of the molecular basis of genetic function. We consider the study of the chemistry of p‐RNA as etiologically relevant in the sense that knowledge of its structural, chemical, and informational properties on the chemical level offers both a perspective and reference points for the recognition of specific structural assets of the RNA structure that made it the (supposedly) superior system among possible alternatives and, therefore, the system that became part of biology as we know it today. The paper describes the chemical synthesis of β‐d‐ (and L)‐ribopyranosyl‐(4′→2′)‐oligonucleotide sequences, presents a resume of their structural and chemical properties, and cautiously discusses what we may and may not have learned from the pyranosyl isomer of RNA with respect to the conundrum of RNA's origin.
Nizatidine for the treatment of patients with quetiapine‐induced weight gain
Authors: Atmaca Murad , Kuloglu Murat , Tezcan Ertan , Ustundag Bilal , Kilic Nulufer 
Published: January 2004

AbstractIt has been reported that nizatidine may reduce weight gain in schizophrenic patients on olanzapine treatment. Leptin has been reported to be associated with antipsychotic‐induced weight gain. Thus, the purpose of the study was to evaluate whether nizatidine might be useful for the treatment of quetiapine‐induced weight gain. Among the patients on the quetiapine monotherapy, 47 participated in the study for the two and half months of the open‐label screening period. However, 28 patients who gained considerable weight in this period entered the 8‐week, double‐blind and placebo‐controlled phase. These patients were randomly divided into two groups; quetiapine plus nizatidine (group I) and quetiapine plus placebo (group II) for the 8‐week double‐blind phase. The patients were evaluated at the baseline and at week 8 with respect to the positive and negative syndrome scale, body mass index, weight and serum leptin levels. The mean weight and leptin levels exhibited modest increases in both groups for the open‐label screening period. In the double‐blind period, in group I, a minimal, but not statistically significant, decrease in weight was observed, with a mean of 1.0 ± 0.6 kg. The weight increased in group II. The leptin levels decreased by a mean of 0.6 ± 0.6 ng/ml in group I, and increased by 1.0 ± 0.9 ng/ml in group II. At evaluation at week 8, a trend toward statistical significance in the mean serum leptin levels between groups was detected. The results suggest that nizatidine treatment may stop but not reduce the weight gain and is correlated with leptin levels in patients with schizophrenia on quetiapine treatment. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of glucose on tobacco withdrawal symptoms in recent quitters using bupropion or nicotine replacement
Authors: McRobbie Hayden , Hajek Peter 
Published: January 2004

AbstractRationale and objectivesGlucose has been shown to alleviate the desire to smoke in abstaining heavy smokers and to increase 1‐month abstinence rates on its own as well as when combined with nicotine patches. It is not known whether a single dose of glucose can provide additional withdrawal relief in patients who have already abstained for a period of time, and whether it can assist patients using bupropion.MethodsSeventy‐five volunteers from a smoking cessation clinic who maintained 1 week of validated continuous abstinence were randomized to receive four 3 mg dextrose or placebo (sorbitol) tablets. There were 31 bupropion and 44 NRT users. Measures of desire to smoke and of five withdrawal symptoms were taken before taking the tablets, and then at 5 min intervals for 20 min.ResultsDespite low baseline ratings of withdrawal discomfort, glucose tablets significantly reduced irritability and hunger in bupropion users. Two other effects including reduction in composite withdrawal score approached but did not reach statistical significance. The effects emerged 10–15 min after taking the tablets. No glucose effect was detected in patients using NRT.ConclusionsA single dose of glucose taken after a week of sustained abstinence may reduce withdrawal discomfort in patients on bupropion. Further research is warranted in combining glucose and bupropion, and in opportunistic use of glucose tablets in tempting situations during a smoking cessation attempt. Copyright © 2004 John Wiley & Sons, Ltd.
Olanzapine treatment of eight adolescent patients with psychosis
Authors: Ercan Eyup Sabri , Kutlu Ayşe , Varan Azmi , Çikoğlu Sibel , Coşkunol Hakan , Bayraktar Erhan 
Published: January 2004

AbstractAlthough olanzapine is known as a widely used atypical antipsychotic there have been very few studies about its use in children and adolescents. Eight adolescent patients who were diagnosed as having schizophrenia or schizoaffective disorder, and treated with olanzapine are reported in this case series. The patients were followed‐up for 17.5 weeks in the range 4–26 weeks. According to the CGI improvement assessment at the end of the follow‐up period, three of eight cases were rated as very much or much improved, three as minimally improved and two as not improved. Olanzapine was well tolerated by the adolescents in this case series except for weight gain. Our results suggest that olanzapine may be an effective antipsychotic for some psychotic adolescents and during olanzapine trials weight gain. Should be monitored. Copyright © 2004 John Wiley & Sons, Ltd.
In vitro microsomal metabolism of imipramine under conditions mimicking the in vivo steady‐state situation
Authors: Linnet Kristian 
Published: January 2004

AbstractA steady‐state model is presented of the metabolism of imipramine. In this model, the N‐demethylation and 2‐hydroxylation rates of imipramine were measured with and without the presence of metabolites by using a tritium isotope of imipramine. At an imipramine concentration of 5 μmol/l, desipramine, in the concentration ratio 1:2, decreased the total metabolic rate by 70%. The 2‐hydroxylation pathway was mainly inhibited, thereby increasing the N‐demethylation pathway from 25% to 62% in the presence of desipramine. The additional presence of 2‐hydroxy‐imipramine did not change this situation. A study on the relative influence of CYP1A2 and 3A4 only revealed minor changes in the presence of desipramine. In conclusion, the presence of metabolites in metabolism studies undertaken in vitro may reflect the changes from the single‐ to the multiple‐dose situation observed clinically and therefore constitute a better model for the clinical application of a drug. Copyright © 2004 John Wiley & Sons, Ltd.
The treatment of depression with different formulations of venlafaxine: a comparative analysis
Authors: Olver James S. , Burrows Graham D. , Norman Trevor R. 
Published: January 2004

AbstractVenlafaxine is the first of a group of antidepressants that show dual reuptake inhibition of serotonin and noradrenaline (SNRIs). Originally marketed in an immediate release (IR) formulation a microencapsulated, extended release (XR) formulation is now available. Significant differences exist between these two formulations with respect to pharmacokinetic parameters which have an impact on clinical use. The XR has lower maximum plasma concentrations (Cmax) and achieves these at a later time (higher Tmax). The longer apparent elimination half‐life of the drug after single XR doses suggests that it is suitable for once daily dosing compared with the twice daily dosing regimen required by the IR formulation. With respect to antidepressant efficacy the XR formulation is equivalent to other marketed antidepressants and to the IR formulation. Consistent with its pharmacokinetic properties the use of the XR formulation is associated with less nausea and dizziness at the initiation of therapy. While in clinical usage XR might be expected to increase compliance with medication and to reduce discontinuation syndromes there are few comparative studies for which this has been evaluated. The XR formulation of venlafaxine is no worse than the IR form with respect to tolerability and offers some benefits to patients in terms of ease of use. On the other hand there does not appear to be any increase in the efficacy of the active agent. Copyright © 2004 John Wiley & Sons, Ltd.
Double‐blind comparative study of the action of repeated administration of milnacipran versus placebo on cognitive functions in healthy volunteers
Authors: Poirier M. F. , Galinowski A. , Amado I. , Longevialle R. , Bourdel M. C. , Tournoux A. , Serre C. , Loo H. 
Published: January 2004

AbstractObjectiveThe principal objective was to compare the effects of milnacipran, an antidepressant characterized by a dual‐action on serotonin and noradrenaline reuptake, with placebo on memory, attention and psychomotor performance in healthy volunteers. The secondary objective was to evaluate the effects of milnacipran on mood, anxiety and vigilance in these subjects.MethodsIn a double‐blind crossover randomized trial, milnacipran (50 mg b.d.) or placebo was administered during two periods of 7 days separated by a washout period of 7 days. Memory tests (recall of words, images and coloured bars), tests to evaluate attention and vigilance (squares test, critical flicker fusion test and choice reaction time test) and visual analogue scales for affect and sleep were used.ResultsThere were no significant differences between milnacipran and placebo groups with respect to the psychomotor functions tested. No differences were observed in the Norris scales for vigilance, anxiety or satisfaction or in the sleep questionnaire (sleep latency, sleep quality and waking).ConclusionMilnacipran, administered at 100 mg per day for 7 days to healthy volunteers, had no effects on cognitive functions. Copyright © 2004 John Wiley & Sons, Ltd.
P16INK4a as an adjunct marker in liquid‐based cervical cytology
Authors: Sahebali Shaira , Depuydt Christophe E. , Segers Kurt , Moeneclaey Liliane M. , Vereecken Annie J. , Van Marck Eric , Bogers Johannes J. 
Published: January 2004

AbstractCytological screening for cervical cancer is hampered by high false negative rates. Inter‐observer reproducibility needs optimizing. The potential of p16INK4a as a biomarker for cervical lesions was examined in a study of liquid‐based cytology (LBC), HPV DNA testing by MY09/MY11 consensus PCR and type‐specific PCRs and p16INK4a immunocytochemistry on a series of 291 patients selected from routine screening. Comparison of the number of p16INK4a immunoreactive cells/1,000 cells exhibited a significantly higher mean count in HSIL (8.80 ± 1.13) than other cytological groups. The mean count of LSIL (1.09 ± 0.18) was significantly higher than that of the negative group (0.82 ± 0.40). ASC‐H and HSIL combined showed a significantly higher mean count (6.46 ± 1.17) than negative, ASC, ASC‐US and LSIL. The mean count of immunoreactive cells/1,000 cells was significantly higher in HPV16 positive samples (3.22 ± 0.72) than in samples containing infections with types of unknown malignant potential (0.83 ± 0.26) or HPV negative samples (1.17 ± 0.41). The mean count in infections with other high‐risk HPV types (2.55 ± 0.52) was significantly higher than that in HPV negative samples. Receiver‐operating characteristic curves yielded a test accuracy (area under curve) of 0.76, 0.79, 0.88 and 0.95 for ASCUS, LSIL, ASC‐H/HSIL and HSIL, respectively. Thresholds for 95% sensitivity were at 0.005, 0.007, 0.098 and 0.445 immunopositive cells/1,000 cells for ASCUS, LSIL, ASC‐H/HSIL and HSIL, respectively. The 95% specificity threshold for the detection of HSIL was at 1.87 immunopositive cells/1,000 cells. P16INK4a immunocytochemistry can be used as an adjunct to LBC in cervical screening, because it has a good diagnostic accuracy to discriminate HSIL and ASC‐H from other lesions. It could be used as a surrogate marker of high‐risk HPV infections. © 2003 Wiley‐Liss, Inc.
Effect of vitamin D analog (1α hydroxy D5) immunoconjugated to Her‐2 antibody on breast cancer
Authors: Punj Vasil , Graves Jewell M. , Mehta Rajeshwari R. 
Published: January 2004

AbstractWe previously showed that a new vitamin D analog, 1α(OH)D5 (D5), induced differentiation and inhibited the growth of breast cancer cells. In this report, we examined whether D5 specifically delivered to breast cancer cells could have any therapeutic effect. D5 was linked to Her‐2 antibody using sulfosuccinimidyl 6‐4 azido nitrophenylamido hexanode (SANPAH) as a linker. The Her‐2 antibody selected in our study had no significant effect on the in vitro or in vivo growth of breast cancer cells; however, it had cell‐differentiating action. In vitro, D5‐Her‐2 antibody conjugate (IMC) showed the ability to specifically bind to Her‐2‐expressing cells, to compete with Her‐2 antibody for surface receptor and to cause internalization. IMC (equivalent to 5 μg Her‐2 antibody given intraperitoneally once weekly for 6 weeks) significantly inhibited the growth of BT‐474 cells transplanted into athymic mice. The in vivo growth‐inhibitory effect of IMC treatment was similar to that observed in animals receiving D5 continuously as a dietary supplement. These results show that the targeted delivery of D5 by immunoconjugation to cell surface receptor antibodies may be of potential therapeutic value for the treatment of Her‐2 positive breast cancer. © 2003 Wiley‐Liss, Inc.