bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and distribution of N‐benzyloxycarbonyl‐[14C]‐glycine, a lipophilic derivative of glycine
Authors: Lambert Didier M. , Gallez Bernard , Poupaert Jacques H. 
Published: October 2006

AbstractN‐benzyloxycarbonyl[14C]‐glycine, a lipophilic derivative of glycine exhibiting anticonvulsant properties, was prepared in one step from [U‐14C] glycine and benzyl chloroformate in alkali medium. A comparative study of biodistribution was carried on mice between this compound and the parent amino‐acid after intravenous administration. Dimethylsulfoxide was used as injection vehicle for N‐benzyloxycarbonylglycine. The influence of this injection vehicle was studied comparing glycine injected in a saline solution and glycine co‐administered with dimethylsulfoxide. No significant difference was found between these two treatments. Compared to glycine, N‐benzyloxycarbonylglycine reached quickly the central nervous system and exhibited an enhanced brain penetration index, 13‐fold superior to the parent aminoacid value.
A preparation of high specific activity [11,12‐3H]‐9‐cis‐retinoic acid
Authors: Coe Jotham W. , Hawes Calvin R. , Towers Patrick 
Published: October 2006

AbstractA selective total synthesis of [11,12‐3H]‐9‐cis‐retinoic acid 1 at a specific activity of 46 Ci/mmole is described. The alkyne 4, efficiently prepared in two steps from readily available starting materials, was partially reduced to 9,11‐di‐cis‐retinoic acid 3 with both deuterium and tritium gas. Selective isomerization of 3 to 1 is discussed, as well as non‐selective direct conversions of 4 to 1.
Methine‐selective deuteration of V(acac)3, [Co(acac)2]4, and Al(acac)3
Authors: Ryan Daniel E. , Nakanishi Koji 
Published: October 2006

AbstractIn solid state NMR studies of transition metal acetylacetonate complexes, peak assignments required complexes deuterated at methine or methyl positions. The preparation of methine‐deuterated complexes—V(acac‐3‐2H)3, [Co(acac‐3‐2H)2]4, and Al(acac‐3‐2H)3—is presented. This method is applicable to preparations of methyl‐deuterated complexes as well.
Synthesis of [11C](−)‐α,α‐dideutero‐phenylephrine for in vivo kinetic isotope studies
Authors: Del Rosario R. B. , Wieland D. M. 
Published: October 2006

Abstract(−)‐[11C]Phenylephrine and positron emission tomography could potentially be used to assess neuronal monoamine oxidase activity in the heart. Previous data for (−)‐(11C]phenylephrine indicate that, although its retention and neuronal selectivity parallel that of the neuronal mapping agent (−)‐[11C]hydroxyephedrine, its neuronal storage and clearance properties are quite different. In order to study the in vivo kinetics of (−)‐[11C]phenylephrine in greater detail, the dideutero analog [11C]‐(−)‐α,α‐dideutero‐phenylephrine, 1, was synthesized by [11C]methylation of the precursor (−)‐α,α‐dideutero‐m‐octopamine. The key step in the procedure was BD3 reduction of the cyanohydrin derived from 3‐hydroxybenzaldehyde. Deuterium incorporation at the alpha positions of m‐octopamine was confirmed by NMR and mass spectroscopy of the deuterated product and by comparison of spectral data with undeuterated m‐octopamine. (−)‐α,α‐Dideutero‐m‐octopamine was methylated with CF3SO311CH3 to give 1 suitable for animal and clinical studies.
An improved synthesis of [amino‐15N]adenine; useful in the large scale synthesis of 2′‐deoxy[amino‐15N]adenosine
Authors: Kelly Joe , Ashburn David A. , Michalczyk Ryszard , Silks Louis A. 
Published: October 2006

Abstract2′‐Deoxy[Amino‐15N]Adenosine has been constructed in two steps from commercially available starting materials. These reactions have been scaled up to give 5 gram lots of labeled material.
Synthesis of carbon C‐14 labelled 2‐phenyl‐4‐alpha‐alkylaminomethyl‐quinolinemethanol: A potential anti‐leishmaniasis agent
Authors: Wang Theodore S. T. , Fawwaz Rashid A. , Van Heertum Ronald L. 
Published: October 2006

AbstractUsing sodium acetate, [1‐14C] as a starting material, a total of seven steps were required to synthesize the title compound. This involved acylation of ortho‐dichlorobenzene to form dichloroacetophenone, [2‐14C] (I). The 2‐phenyl‐4‐quinoline carboxylic acid, [2‐14C] (II) was prepared by the Pfitzinger reaction from (I) and dichloroisatin. Compound II was converted to the acid chloride (III) by reaction with SOCl2 in benzene. Grignard condensation reaction of (III) yielded 4‐quinolylmethylketone, [2‐14C] (IV) which was then converted to the bromomethylketone (V). Compound V was reacted with NaBH4 to form the ethylene oxide (VI). Alkylation of the oxide yielded the title compound (VII). The overall radiochemical yield was 10.1% and the specific activity was 3.0 mCi/mmol, with a radiochemical purity of > 99.5%.
Synthesis of high specific radioactivity [3H]emodin
Authors: Hadj‐Hamdri Aziz , Vidal‐Cros Anne , Gaudry Michel , Sobrio Franck , Rousseau Bernard 
Published: October 2006

AbstractEmodin, a precursor of chrysophanol in the biosynthesis of cynodontin by Pyrenochaeta terrestris, has been tritiated with a high specific radioactivity (12.5 Ci/mmol) by hydrogenolysis of bromomethyl emodin.
Marquages par [14C] et [13C] de la N‐(2‐diéthylaminoéthyl)‐4‐iodobenzamide et de la N‐(3‐diméthylaminoprophyl)‐4‐iodobenzamide, traceurs du mélanome
Authors: Moreau M. F. , Parry D. , Bayle M. , Papon J. , Labarre P. , Veyre A. 
Published: October 2006

AbstractN‐(2‐diethylaminoethyl)‐4‐iodobenzamide (I) and N‐(3‐dimethylaminopropyl)‐4‐iodobenzamide (II), recently developed in our laboratory, are promising agents for metastatic melanoma detection in nuclear medicine. In order to study their “in vivo” metabolism, we labelled them with carbon‐14 and carbon‐13 on two sites: on the carbonyl group (Ia, IIa), and on the dialkylaminoalkyl moiety (Ib, IIb). The overall yields calculated from sodium [14C] or [13C] cyanide used as precursor are in the range of 55% for Ia, IIa, IIb, and 21% for Ib.
Synthesis of mixed halogenated trihalomethanes labelled with the stable isotopes 2H or 13C
Authors: Vermeulen H. L. , Sangaiah R. , Ball L. M. , Gold A. 
Published: October 2006

Abstract2H and 13C‐labelled bromodichloromethane and chlorodibromomethane were obtained in yields of 20 and 12% (for 2H) and 6 and 3% (for 13C) respectively from a convenient aluminum chloride‐catalyzed reaction of bromoethane with commercially‐available isotopically‐substituted chloroform. The products were purified by preparative gas chromatography and characterized by MS and 13C NMR, and by 1H for the 13C‐labelled material; mass and nuclear magnetic resonance spectroscopy data are reported.
Synthesis and receptor binding of 5‐amino[3H]2methyl‐3‐isothiazolol ([3H]thiomuscimol), a specific GABAa agonist photoaffinity label
Authors: Frølund B. , Ebert B. , Lawrence L. W. , Hurt S. D. , Krogsgaard‐Larsen P. 
Published: October 2006

AbstractThe synthesis of tritium labelled thiomuscimol(5‐amino[3H]2methyl‐3‐isothiazolol) (7c), a specific and high‐affinity agonist photoaffinity label for GABAA receptors, is described. The synthesis of 7c is based on a procedure for the preparation of 5‐amino[2H]2methyl‐3‐isothiazolol (7b). Methyl 3‐ethoxyisothiazole‐5‐carboxylate (3), synthesized from 3‐hydroxyisothiazole‐5‐carboxamide (1) via the corresponding methyl ester (2), was reduced with sodium borotritide to give 3‐ethoxy‐5‐hydroxy[3H]2methyl‐3‐isothiazole (4c). 3‐Ethoxy‐5‐phthalimido[3H]2‐methylisothiazole (6c), synthesized from the 5‐chloro[3H]2methyl analogue (5c) of (4c), was deprotected by treatment with concentrated hydrochloric acid to give 7c with a specific radioactivity of 29 Ci/mmol. In pilot binding assays, 7c was shown to bind to membranes from rat forebrain in a saturable manner and with KD and Bmax values of 28 ± 6 nM and 50 ± 4 fmol/mg original tissue, respectively.
Synthesis of deuterated mosapride citrate
Authors: Kato Shiro , Hirokawa Yoshimi 
Published: October 2006

AbstractThe deuterium labeled form of mosapride citrate, a potential gastroprokinetic agent, was prepared via reduction of ethyl 4‐(4‐fluorobenzyl)‐2‐morpholinecarboxylate (4) with lithium borodeuteride.
The synthesis of [fluorophenyl‐3H(N)] ocfentanil and [fluorophenyl‐3H(N)] brifentanil
Authors: Filer C. N. , Nugent R. P. , Huang B. S. 
Published: October 2006

Abstract[Fluorophenyl‐3H(N)] Ocfentanil (1b) and [fluorophenyl‐3H(N)] brifentanil [2b] were synthesized by catalytic tritiation of appropriate bromo precursors (1a, 2a). The products were purifled by preparative HPLC and characterized chromatographically and by proton decoupled 3H NMR.
Synthesis of carbon‐14 labeled (±) 15‐deoxyspergualin trihydrochloride
Authors: Dischino Douglas D. 
Published: October 2006

AbstractC‐14 labeled (±) 15‐Deoxyspergualin trihydrochloride, 1‐amino‐19‐(14C‐guanidine)‐11‐hydroxy‐4,9,12‐triazanonadecane‐10,13‐dione trihydrochloride was prepared in a 3% overall yield from Carbon‐14 labeled S‐Methyl isothiourea hemisulfate, [imino‐14C]. The radiochemical purity of the sample was 97.0% and the specific activity was 41.3 microcuries/mg.
Astatine‐211 labeling of a monoclonal antibody and its Fab fragment synthesis, immunoreactivity and experimental therapy
Authors: Ning Liu , Jiannan Jin , Shuyuan Zhang , Deyuan Luo , Juan Wang , Maolum Zhou , Lin Luo , Fangyuan Wang 
Published: October 2006

AbstractAn antigastric cancer monoclonal antibody, 3H11 and its Fab fragment, were labelled with a‐emitter 211At using p‐(211At)‐astatobenzoic acid (pAtBA) intermediate, in the yields of more than 30%. The astatinated antibodies were stable in vitro, and had specific immunoreactivity to human gastric cancer cell M85. The therapeutic effect of the astatinated antibodies for subcutaneous xenografts of human gastric cancer were investigated in nude mice by i. p. injection,once every 5 days for 3 times sucessively, with 1.48 × 104 and 2.22 × 104Bq/g of 211At‐3H11 and 211At‐3H11 Fab per injection, respectively. It was showed that the volume and weight of xenografts in all tested groups were much smaller and lighter than that of control group (PBS) from 12.5 days post first injection. The most evident inhibition was observed in the groups with 211At‐3H11 Fab, with tumor inhibility of 67.5‐69.5% at 15 days and 70.7‐72.3% at 20 days, respectively.
Synthesis of a tritium labelled antihistaminic drug [3H]‐N,N‐diethyl‐2‐[4‐(phenylmethyl)phenoxy]‐ethaneamine · HCl
Authors: Kovalainen J. T. , Morimoto H. , Williams P. G. , Vepsäläinen J. , Reijonen A. , Gynther J. 
Published: October 2006

AbstractA tritium labelled antihistamine, N,N‐diethyl‐2‐[4‐(phenylmethyl)phenoxy]‐ ethaneamine · HCl (DPPE, 4) was synthesized to investigate its binding characteristics to intracellular histamine receptors (HIC) and for further studies with specific ligands of HIC to determine their potential effects on cell proliferation. A palladium catalyzed reduction of an activated carbonyl between the two phenyl groups of N,N‐diethyl‐2‐[4‐(benzoyl)phenoxy]‐ethaneamine · HCl (DBPE, 3) with 100% tritium gas was successful, where 55% øf the theoretical activity (specific activity 31.6 Ci/mmol) was obtained.
Synthesis of 13C‐labelled (all‐E,3R,3′R)‐β,β‐carotene‐3,3′‐diol (zeaxanthin) at C(12), C(13), C(12′), and C(13′) via all‐E‐2,7‐dimethylocta‐2,4,6‐triene‐1,8‐dial‐13C4
Authors: Khachik Frederick , Beecher Gary R. , Li Betty W. , Englert Gerhard 
Published: October 2006

AbstractThe title compound (10) has been synthesized from all‐E‐2,7‐ dimethylocta‐2,4,6‐triene‐1,8‐dial (C10‐dialdehyde, 8) labelled with four 13C from commercially available and relatively inexpensive starting materials. The key starting material in this synthesis, (EtO)2P(O)13CHMe13CO2Et (2), has been prepared from triethyl phosphonoacetate‐13C2. The sodium salt of 2 reacted with fumarylaldehyde dimethylacetal to give ethyl 6,6‐dimethoxy‐2‐methyl‐E, E‐2,4‐hexadienoate (4) which was converted to 8 in four steps [(1) acid hydrolysis, (2) 2/NaH, (3) LiAlH4 reduction, (4) MnO2 oxidation]. The overall yield of 8 based on phosphonate 1 is 43‐46%. The double Wittig reaction of 8 with [(3R‐3‐hydroxy‐β‐ionylidene)ethyl]triphenylphosphonium chloride afforded 10 also known as (all‐E,3R,3′R)‐zeaxanthin‐13C4 (39% based on phosphonate 1) in high purity. This synthetic method may be extended to prepare other 13C‐labelled carotenoids.
A facile synthesis of [14C]enadoline [(5R)‐(5α, 7α,8β)]‐N‐methyl‐N‐[7‐(1‐pyrrolidinyl)‐1‐oxaspiro[4.5] DEC‐8‐YL]‐4‐benzofuranacetamide
Authors: Pu Yu‐Ming , Scripko James , Huang Che C. 
Published: October 2006

Abstract4‐Chloromethylbenzofuran (10) was synthesized from 2,3‐dimethylanisole in 7 steps. The corresponding Grignard reagent prepared from magnesium‐anthracene complex reacts with 14CO2, SOCl2, and PD130812 successively to give [14C]enadoline (2), a non‐peptide, selective kappa opioid receptor agonist. This method could be readily modified for the rapid, one‐pot synthesis of [11C]enadoline.
Synthesis of deuterium‐labelled polyoctylalkanes
Authors: Bolton Roger , Luff Stefan , Sutcliffe Leslie H. 
Published: October 2006

AbstractThe synthesis of specifically labelled 9‐d‐9‐octylheptadecane (1) and 9‐d‐9,10‐dioctyloctadecane (2) has been achieved using selective and specific deuterium labelling methods. The precursor to the latter compound, tetraoctyl ethene, has been achieved by a variant of the McMurry reaction which improves upon recently published methods.
Ein intramolekularer isotopeneffekt bei dem ringshluss zu 4H‐pyrido‐ (1, 2‐A) pyrimidin‐4‐onen und 1, 8‐naphtyridinen
Authors: Voford J. , Mészáros Z. , Kovàcs G. 
Published: October 2006

AbstractBei der Kondensation eines an der Carbonyl‐Gruppe mit 14 C markierten Malonester‐Derivates wurde eine durch den kinetischen Isotopeneffekt hervogerufene Fraktionierung beobachtet. Beim Ringschluss sowohl zu 4H‐Pyrido ‐ (1, 2‐a) pyrimidin, als auch zum 1, 8‐Naphtyridin wurde ein mit dem geschätzten Wert (4. 3%) gut übereinetimmender intramolekularer Effekt gemessen.
Site ‐specific deuteration or tritiation of benzo [b] thiophene and 1‐ methylindole analogs of biologically active indole derivatives (1)
Authors: Bosin T. R. , Rogers R. B. 
Published: October 2006

AbstractThe site‐specific deuteration and tritiation of 1‐methylindole and benzo [b] ‐thiopheme analogs of biologically active indole derivatives has been achieved by use of the facile metalation of these heterocycles with n‐butyllithium and subsequent reaction with 2H2 or 3H2O. Metalation occurs at the 2‐position and site and extent of deuterium incorporation was determined by N. M. K. The use of similar procedures with 3H2 O led to ready incorporation of tritium into these heterocycles.
Synthesis of 14C‐labelled 5‐ethyl derivatives of pyrimidine
Authors: Skakun‐Todorovič M. , Jezdič V. 
Published: October 2006

AbstractA method for the synthesis of 5‐ethylorotic acid‐2‐14C (V), 5‐ethyluracil‐2‐14C (VI) and 5‐ethylytosine‐2‐14C (VIII) starting from thiourea‐14C with the specific activity of 30 mCi/mM has been described. The labelled compounds obtained show satisfactory chemical and radiochemical purity. The method was modified and adapted for work at the level 1‐5 mM.
The synthesis of 14C ‐3‐ chloro ‐, 3 ‐ bromo ‐ and 3 ‐ iodo ‐propan ‐ 1, 2 ‐ diol and 2, 3 ‐ epoxypropan ‐ 1 ‐01
Authors: Jones A. R. 
Published: October 2006

AbstractA convenient procedure has been developed for the synthesis of 14C‐3‐chloropropan‐1, 2‐diol (α‐chlorohydrin, I) from 14C‐glycerol which can also be applied to the preparation of 14C‐3‐bromopropan‐1, 2‐diol (α‐bromohydrin, III). These two compounds can be converted, respectively, by nucleophylic displacement with sodium iodide 14C‐3‐iodopropan‐1, 2‐diol (α‐iodohydrin, II) and by alkaline epoxidation to 14C‐2, 3‐epoxypropan‐1‐01 (glycidol, IV). The use of readily available u, 1, 3‐ or 2‐ 14C‐glycerol thus enables the title compounds to be synthesised readily and any desired labelling pattern as useful 3‐carbon intermediates for further radioactive syntheses.
Recent developments in the chromatographic analysis and purification of radioactively laeelled lipids
Authors: Mukherjee K. D. , Mangold H. K. 
Published: October 2006

AbstractMethods for the analysis and purification of lipophilic substances labelled with 3H or 14C are outlined. The necessity of using various techniques based on complementary principles is emphasized. In addition, new developments in instrumentation for the quantitative analysis and preparative isolation of labelled substances are described.
Automation and Optimization of Protein Expression and Purification on a Novel Robotic Platform
Authors: Wollerton Matthew C. , Wales Richard , Bullock Jonathan A. , Hudson Ian R. , Beggs Mark 
Published: October 2006

This article describes a novel robotic system for protein expression and purification. This area has traditionally proved a bottleneck in pharmaceutical discovery owing to the difficulty and unpredictability of outcome in evaluating multiple sets of expression conditions that will yield biologically active protein in sufficient quantity to meet the demands of discovery teams. This position has been exacerbated by the requirement of structural biology groups to have access to 100 mg scale quantities of pure protein for early and complex structural studies. The Piccolo robotic system described here was able to perform multiple parallel induction, expression, and single stage protein purification of a target protein (6-His tagged β-galactosidase) using a model E. coli expression system. The Piccolo system monitored E. coli cell growth automatically and rescheduled tasks dynamically based on individual instances of cell growth within purpose built 24-well bioreactor units termed culture vessel blocks. On completion of protein expression, the system performed cell lysis and purification of the expressed β-galactosidase through Ni-NTA histidine affinity chromatography. We show that alterations in the induction and expression conditions used resulted in changes in the yield of expressed β-galactosidase. In addition to the E. coli studies described here, the system is also applicable for other bacterial species and for eukaryotic cell culture applications. The Piccolo robotic system has the capacity to allow exploration of hundreds of different combinations of expression variables within a working week thereby allowing rapid identification of optimal conditions for expressing the biologically active protein of interest. This strategy confers a significant increase in the parallel processing capability of protein expression groups and goes a long way to addressing the current protein expression bottleneck.
Inherent limitations in protein–protein docking procedures
Authors: Kowalsman Noga , Eisenstein Miriam 
Published: October 2006

AbstractMotivation: The limited success rate of protein–protein docking procedures is generally attributed to structure differences between the bound and unbound states of the molecules. Herein we analyze a large dataset of protein–protein docking results and identify additional parameters that affect the performance of docking procedures.Results: We find that the distinction between nearly correct models (NCMs) and decoys depends on the size of the interface to be predicted thus setting a limit to the prediction ability of docking procedures, particularly those in which the geometric complementarity descriptor is dominant. The geometric complementarity score in grid-based docking carries a large statistical error which further reduces the distinction between NCMs and decoys. We propose a method for correcting the statistical error and show that the distinction is improved when the docking models are ranked by statistically equivalent scores.Availability: MolFit can be downloaded from our websiteContact: Supplementary information: Supplementary data are available at Bioinformatics online.
Deletion analysis of the p16 tumour suppressor gene in phaeochromocytomas
Authors: Aguiar Ricardo C. T. , Dahia Patricia L. M. , Sill Heinz , Toledo Sergio P. A. , Goldman John M. , Cross Nicholas C. P. 
Published: October 2006

SummaryBACKGROUND AND OBJECTIVES The molecular pathogenesis of phaeochromocytoma has not yet been fully established. The p16 turnour suppressor gene is often inactivated in a wide variety of primary human malignancies, including tumours of ectodermal origin. We have therefore examined the status of the p16 gene in a series of phaeochromocytomas.DESIGN We studied tumour and constitutive DNA from 26 phaeochromocytoma patients. Twenty‐two cases were of sporadic tumours whereas four patients had a hereditary form of the disease. Four tumours were malignant. We performed a semiquantitative multiplex PCR in which the p16 gene was coamplified with an unrelated sequence as an internal control. Standards were constructed by mixing DNA from cell lines with a known p16 status to simulate various degrees of p16 loss. Deletion of the p16 gene was determined by densitometry, measuring the ratio of intensity of the two resulting bands as an indication of the relative abundance of the two templates in the sample.RESULTS No homozygous deletion of the p16 tumour suppressor gene was found in any of the phaeochromocytoma samples.CONCLUSIONS We have demonstrated that the p16 gene is not deleted in sporadic, hereditary, malignant or benign forms of phaeochromocytomas, and therefore probably does not play a role in the pathogenesis of this tumour. However, because of the small number of malignant cases analysed, we cannot exclude a low frequency of p16 deletions in this subset of tumours.
Cardiomyopathy associated with Graves' disease
Authors: Koshiyama Hiroyuki , Sellittl Donald F. , Akamizu Takashi , Doi Sonia Q. , Takeuchi Yuzou , Lnoue Dalsuke , Sakaguchl Hiromi , Takemura Genzou , Sato Yuklhlto , Takatsun Yoshiki , Nakao Kazuwa 
Published: October 2006

SummaryCardiovascular changes associated with Graves' disease are generally considered to be secondary to the increased levels Of thyroid hormone. We describe a case of Graves' disease in a 25‐year‐old man, who developed cardiomyopathy with severe heart failure. Pathological examination of the myocardial biopsies showed fibroblast infiltration and degenerative changes. After the cardiomyopathy subsided the patient developed a goitre and signs of hyperthyroidism, followed by Graves' ophthalmopathy, which was treated successfully with a combination of high‐dose corticosterolds and orbital radiotherapy. These findings suggested a common pathogenesis for the cardiomyopathy and ophthalmopathy, and prompted us to investigate the expression of TSH receptor (TSH‐R) in human heart. TSH‐R mRNA was identified in human heart using the reverse transcriptase‐polymerase chain reaction (RT‐PCR) and DNA sequencing. Taken together, these data suggest that autoimmunity against the TSH‐R mlght contribute to both the cardiomyopathy and ophthalmopathy in similar cases of Graves' disease.