bluuebunny/crossref_metadata_2025 huggingface dataset:
Ester der 99mTc‐markierten cytectren‐carbonsäure mit alkoholen cyclischer amine als gehirn‐affine radiodiagnostika
Authors: Wenzel M. , Saidi M.
Published: October 2006

Esters of ferrocene carbonic acid with aminoalcoholes in the presence of carbonyl donators can exchange their central atom Fe against 99mTc from pertechnetate yielding cytectren‐derivatives. Organ distribution of the 99mTc labelled esters showed a high brain uptake.
Chemoenzymatic synthesis of carbon‐14 labelled antioxidants
Authors: Deigner H. P. , Freyberg C. , Heck R.
Published: October 2006

The syntheses of [14C] labelled antioxidants are described. We developed an efficient synthetic methodology to prepare a series of labelled amides with antioxidant activity, starting from [14C] KCN and alkyl or aryl halides. By a combination of nucleophilic displacement of halides by [14C] cyanide, mediated by ultrasound and subsequent mild and selective enzymatic hydrolysis of the resulting nitriles, labelled carboxylic acids were obtained. Labelled amines were prepared by reduction of the respective nitriles. Availability of [14C] KCN, efficient introduction of the label by ultrasound mediated reaction and selective and mild hydrolysis by comercially available nitrilase (Rhodococcus sp.), makes possible a wide range of applications of this methodology in the synthesis of functionalized labelled compounds.
Synthesis and NMR study of [4,5,6,8‐2H4][2.2]metacyclophane
Authors: Tsuzuki Hirohisa , Kamio Katsuhiko , Fujimoto Hideki , Mimura Keisuke , Matsumoto Susumu , Tsukinoki Takehito , Mataka Shuntaro , Yonemitsu Tadashi , Tashiro Masashi
Published: October 2006

The synthesis of [4,5,6,8‐2H4][2.2]metacyclophane (8) was achieved starting with 2,4,5,6‐tetrafluoroisophthalic acid in eight steps in 2% total yield. 1H{2H} and 13C{1H} NMR spectra of 8 showed that the deuterium atoms were introduced at the desired positions.
Indolealkylamine metabolism: Synthesis of deuterated indolealkylamines as metabolic probes
Authors: Morris Philip E. , Chiao Cheng
Published: October 2006

The synthesis of the deuterium labeled, endogenously occurring, indolealkylamine hallucinogens N,N‐dimethyltryptamine and 5‐methoxy‐N,N‐dimethyltryptamine via reduction of amide intermediates with lithium aluminum deuteride is described. The compounds were characterized with 1H, 2H and 13C NMR. These compounds were synthesized for use as probes for investigating the metabolism of these compounds by MAO via the in vivo kinetic isotope effect.
Can we predict reactivity for aromatic nucleophilic substitution with [18F]fluoride ion?
Authors: Rengan Ramesh , Chakraborty Pulak K. , Kilbourn Michael R.
Published: October 2006

The correlation between the 13C‐NMR chemical shift of the aromatic ring carbon bearing the leaving group and the yield of nucleophilic aromatic displacement with no‐carrier‐added [18F]fluoride ion was evaluated. In comparison of structurally analogous compounds (fluoro, nitro and trimethylammonium substituted benzaldehydes, benzophenones and benzonitriles), the 13C‐NMR chemical shift of the reactive aryl ring carbon correlated quite well with the [18F]fluorination yield (r2=0.87) for most but not all ring structures. Compounds with trimethylammonium leaving groups or methyl ring substituents were found to not fit the proposed correlation. Kinetic studies indicated clearly different rates of reaction for these compounds, with much higher than expected reactivity for the ccompounds with the cationic leaving group. Competition experiments suggest that low reactivity of methyl‐substituted rings may be due to conversion of [18F]fluoride to an unreactive form. Our results indicate that the correlation between [18F]fluorination yields for nucleophilic aromatic substitution reactions and the 13C NMR chemical shift of the aryl ring carbon bearing the leaving group is applicable to numerous structurally analogous compounds, but cannot be simply generalized to aromatic rings with different leaving groups or ring substituents.
A rapid synthesis of [fluoroacetyl‐18F]fluoromelatonin (Nω‐[18F]fluoroacetyl‐5‐methoxytryptamine), a potential diagnostic imaging agent
Authors: Tada Masao , Iwata Ren , Sugiyama Hiroshi , Sato Kazunori , Pascali Claudio , Fukuda Hiroshi , Kubota Kazuo , Kubota Roko , Takahashi Hiromu , Wakui Akira , Abe Yoshinao , Fujiwara Takehiko , Sato Tachio , Ido Tatsuo
Published: October 2006

An efficient synthesis of [fluoroacetyl‐18F]fluoromelatonin (Nω‐[18F]Fluoroacetyl‐5‐methoxytryptamine) starting from [18F]fluoride and ethyl p‐toluensulfonyloxyacetate is described. The total time required for its synthesis is ca. 90 min. The radiochemical yield, purity and specific activity (end of bombardment) of the desired compound are 14.2%,>98%, and 540 mCi/μmol, respectively.
Rapid, regiospecific syntheses of deuterium substituted 6‐[18F]fluorodopamine (α,α‐D2; β,β‐D2 and α,α,β,β‐D4) for mechanistic studies with positron emission tomography
Authors: Ding Yu‐Shin , Fowler Joanna S. , Wolf Alfred P.
Published: October 2006

Doubly labeled (18F and deuterium) 6‐fluorodopamine (6‐FDA) isotopomers were prepared to probe the contribution of metabolism by monoamine oxidase (MAO) and dopamine β‐hydroxylase (DBH) on the kinetics of 6‐[18F]FDA in baboon heart. Specifically deuterated 6‐[18F]FDA‐α,α‐D2 and 6‐[18F]FDA‐β,β‐D2 were prepared by a six‐step synthesis starting from nucleophilic aromatic substitution with NCA [18F]fluoride on 6‐nitropiperonal or 6‐nitropiperonal‐D in a decay corrected radiochemical yield of 3‐10% (EOB). 6‐[18F]FDA‐α,α,β,β‐D4 was prepared in 4 steps in a radiochemical yield of 16‐20% (EOB) and specific activity 2‐5 Ci/μmol (EOB). The regiospecificity of deuterium substitution in the synthesis of 6‐[18F]FDA‐α,α,β,β‐D4 was verified using piperonal as a substrate.
The Synthesis of [methylenedioxy‐14C]paroxetine BRL 29060A
Authors: Lawrie K W M , Rustidge D C
Published: October 2006

Paroxetine (1), BRL 29060A, a potent antidepressant, has been prepared radiolabelled with carbon‐14 in the methylenedioxy group in 5 steps and 20.9% overall yield from [14C]dibromomethane. Two altenative preparations of 3,4‐[methylenedioxy‐14C]phenol (2) are also described.
Syntheses of 9‐(2′‐monoethylphosphonomethoxyethyl)‐8‐[14C]guanine ([14C]‐EPMG) and 9‐(2′‐phosphonomethoxyethyl)‐8‐[14C]guanine ([14C]‐PMEG)
Authors: Haynes U. J. , Swigor J. E.
Published: October 2006

The synthesis of the title compounds [14C]‐PMEG (5) and [14c]‐EPMG (6) are described. Treatment of [14C]guanine with acetic anhydride in 1‐methyl‐2‐pyrrolidinone gave [14C]N‐acetylguanine (2). Reaction with 2‐(diethylphosphonomethoxy) ethylmethanesulfonate in N,N‐dimethylformamide in the presence of potassium carbonate yielded 2‐N‐acetyl‐9(2′‐diethylphosphonomethoxyethyl)‐8‐[14C]‐guanine (3). Removal of the acetyl group with aqueous methylamine gave 9‐(2′‐ (diethylphosphonomethoxyethyl)‐8‐[14C]‐guanine (4). Treatment of the diethylphosphonate ester with sodium hydroxide and acidification with hydrochloric acid gave 9‐(2′‐(monoethylphosphonomethoxyethyl)‐ 8‐[14C]‐guanine (5). Silation of the diethylphosphonate ester with bromotrimethylsilane and treatment with water produced 9‐(2′‐phosphonomethyloxethyl)‐8‐[14C]guanine (6).
Radiolabelled amino acids: Synthesis of NG‐mesitylenesulfonyl‐N2‐[3H]methyl‐arginine
Authors: Landvatter Scott W.
Published: October 2006

The N2‐methyl amino acid NG‐mesitylenesulfonyl‐[3H]methylarginine has been prepared in high specific activity tritium labelled form by treating methyl N2‐2,4‐dimethoxybenzyl‐NG‐mesitylenesulfonyl‐arginate with [3H]methyl iodide and silver(I) oxide. Removal of the dimethoxybenzyl group by transfer hydrogenation (4.4% formic acid in methanol/Pd black) followed by saponification gave NG‐mesitylenesulfonyl‐[3H]methylarginine in 30‐38% overall from [3H]methyl iodide. This amino acid was ultimately used in the preparation of tritium labelled SK&F 107260 which is a cyclic peptide showing fibrinogen receptor antagonism.
Synthesis of D,L‐[2‐15N,5‐13C]glutamic acid
Authors: Laiuppa John C. , Lemaster David M.
Published: October 2006

A one‐pot procedure is described for the synthesis of D,L‐[2‐15N,5‐13C]glutamic acid from 2‐bromo‐4–butyrolactone utilizing potassium 15N‐phthalimide and potassium 13C‐cyanide as label sources. Following a two column purification procedure, the final product is obtained in 38% yield based on the equimolar label sources.
Synthesis of α‐[14C]methyl and α‐[3H]methyl‐L‐tryptophan
Authors: Venkatachalam T. K. , Mzengeza S. , Diksic M.
Published: October 2006

The title compounds were synthesized starting from dimethyl (2S,3aR,8aS)‐(+)‐8‐(phenylsulfonyl)hexahydrophyrrolo[2,3‐b]indole‐1,2‐dicarboxylate. This compound on treatment with LDA followed by reaction with [14C]methyl iodide or [3H]methyl iodide gave the methyl substituted derivative which on treatment with trifloroacetic acid followed by hydrolysis with alkali gave the desired α‐[14C]methyl‐ or [3H]methy‐L‐tryptophan, respectively, in 50‐60% radiochemical yield.
Tc‐99m und deuterium markierte gehirn‐affine radiodiagnostika ‐ vergleich von HMPAO mit cytectren‐derivaten cyclischer amine
Authors: Wenzel M. , Klinge C. , Saidi M.
Published: October 2006

HMPAO‐d2 and Deuterium labelled esters of Cytectrenecarbonic ester with alcohols of cyclic amines were synthesized and additional labelled with Tc‐99m. The organ distribution in rats showed a higher brain uptake of the cytectrene ester than HMPAO with a far higher Tc‐99m concentration ratio brain/blood.

The deuterated compounds showed a lower Tc‐99m concentration in blood, but no higher uptake in brain.
Radiosynthesis of a photoaffinity probe for the cocaine receptor of the dopamine transporter: 3β‐(p‐chlorophenyl)tropan‐2β‐carboxylic acid m‐([125I]‐iodo)‐p‐azidophenethyl ester ([125I]‐RTI‐82)
Authors: Lever John R. , Carroll F. Ivy , Patel Amrat , Abraham Philip , Boja John , Lewin Anita , Lew Robert
Published: October 2006

The tropane alkaloid RTI‐82, an iodoarylazide, has been labeled with iodine‐125 for use as a photoaffinity probe for the cocaine binding site of the dopamine transporter. The one‐flask radiosynthesis involves nocarrier‐added electrophilic radioiodination of the corresponding aniline followed by diazotization and treatment with sodium azide. Isolation by reverse phase HPLC and solid phase extraction gives [125I]‐RTI‐82 in good yield (76 ± 7%, n=6), high radiochemical purity (>99.8%), and high specific radioactivity (1490 ‐ 1880 mCi/μmol).
Synthesis of [β,β,γ,γ,δ,δ,δ,–2H7]‐n‐butylbenzene
Authors: Kendall John T. , Spencer Thomas A.
Published: October 2006

A convenient preparation of [β,β,γ,γ,δ,δ,δ–2H7]‐n‐butylbenzene has been achieved by base‐catalyzed isotopic exchange of 4‐phenyl‐2‐butanone followed by application of Vedejs' procedure for Clemmensen reduction in a deuteriated medium.
Synthesis of [14C]CI‐980, ethyl [5‐amino‐1,2‐dihydro‐2(S)‐methyl‐3‐[14C]phenylpyrido[3,4‐ 6]pyrazin‐7‐YL]carbamate isethionate salt, a tubulin‐binding, antimitotic, broad‐spectrum antitumor agent
Authors: Woo Peter W. K. , Lee Helen T.
Published: October 2006

[14C]CI‐980 (14b) was synthesized in eight steps starting from [U‐14C]benzene (5), which was converted to bromo[14C]benzene (6) in the presence of tetrabutylammonium bromide as catalyst. Reaction of 6 with the anion of N‐ethoxycarbonyl‐N′‐methoxy‐N′‐methyl‐L‐alaninamide (4a) gave the chiral (S)‐ketone 8 with ee exceeding 96%. Sodium borohydride reduction of 8, followed by sequential condensation with ethyl 6‐amino‐4‐chloro‐5‐nitro‐2‐pyridine carbamate (11), chromium trioxide oxidation, and catalytic hydrogenation over Raney nickel gave the free base form of [14C]CI‐980 (14a), which was extremely unstable and readily aromatized to 15. The free base 14a was, however, isolated under specially developed conditions and converted to the crystalline isethionate salt 14b in pure form.
Synthesis of [3H]CI‐980, ethyl[5‐anino‐1,2‐dihydro‐2(S)‐methyl‐3(3‐[3H]phenyl)pyrido[3,4‐b]jpyrazin‐7‐YL] carbamate isethionate salt, a tubulin‐binding, antimitotic, broad‐spectrum antitumor agent
Authors: Lee Helen T. , Woo Peter W. K.
Published: October 2006

[3H]CI‐980 (10b) was synthesized in an eight‐step sequence with an overall yield of 2.4%. Reaction of m‐bromophenyl lithium (2) with N‐ethoxycarbonyl‐L‐alanine gave the chiral ketone 3. Reduction of 3 with sodium borohydride followed by alkaline N‐deprotection and condensation with ethyl 6‐amino‐4‐chloro‐5‐nitro‐2‐pyridine carbamate (6) gave 7. Chromium trioxide oxidation of 7 followed by reductive cyclization with iron‐acetic acid gave the key bromo intermediate 9. Palladium catalyzed 3H‐hydrogenolysis of 9 gave the free base form of [3H]CI‐980 (10a), which was converted to the isethionate salt (10b) before use.
Synthesis of 5‐fluoro‐3‐[3‐[4‐(2‐[14C]‐5‐methoxy‐4‐pyrimidinyl)‐1piperazinyljpropypiperazinyl]propyl]‐1H‐indole dihydrochloride
Authors: Haynes Ute J. , Swigor J. E.
Published: October 2006

The synthesis of 5‐Fluoro‐3‐[3‐[4‐(2‐[14C]‐5‐methoxy‐4‐pyrimi‐dinyl)‐1‐piperazinyl]propyl]‐1H‐indole dihydrochloride (5) was achieved by coupling [14C] formamidine acetate (1) and dimethylmethoxymalonate in methanol containing sodium methoxide at 60°C to provide 2‐[14C] 4,6‐dihydroxy‐5‐methoxyprimidine (2). Reaction of (2) with phosphorous oxychloride produced the unstable chloro‐compound (3) which was reacted with 5‐Fluoro‐3‐(3‐N‐piperazinylpropyl) indole to give 5‐Fluoro‐3[3‐[4‐(2‐[14C]‐6‐chloro‐5‐methoxy‐4‐pyrimidinyl)‐1‐piperazinyl] propyl]‐1H‐indole (4). Catalytic reduction of (4) and addition of 2 equivalents of hydrochloric acid resulted in the title compound as the dihydrochloride (5).
Synthesis of 3H‐ and 14C‐labelled CP‐88,059: A potent atypical antipsychotic agent
Authors: Howard Harry R. , Shenk Kevin D. , Smolarek Teresa A. , Marx Michael H. , Windels James H. , Roth Robert W.
Published: October 2006

The syntheses of 3H‐ and 14C‐labelled CP‐88,059 [i.e., 5‐(2‐(4‐(1,2‐benzisothiazol‐3‐yl)piperazinyl)ethyl)‐6‐chloro‐1, 3‐dihydro‐2H‐indol‐2‐one] are described. CP‐88,059 (5b) is a combined D2/5‐HT2 antagonist currently undergoing clinical evaluation as an antipsychotic agent with reduced potential for induction of EPS in schizophrenic patients. Displacement of bromine from the 7‐position of the benzisothiazole moiety, by reductive dehydrogenation with tritium gas and Pd/BaSO4 catalysis, provided 3H‐CP‐88,059 (5c). Incorporation of 14C into the ethylene portion of the molecule was achieved via the Friedel‐Crafts acylation of 6‐chlorooxindole with [2‐14C]‐chloroacetyl chloride, followed by triethylsilane reduction of the aryl carbonyl and coupling with N‐(1,2‐benzisothiazol‐3‐yl)piperazine in refluxing aqueous Na2CO3.
Synthesis of 17O (and 18O) labelled isophosphoramide mustard
Authors: Han Sung Y. , Shulman‐Roskes Ellen M. , Misiura Konrad , Anderson Lawrence W. , Szymajda Edward , Gamcsik Michael P. , Chang Young H. , Ludeman Susan M.
Published: October 2006

The ifosfamide metabolite isophosphoramide mustard (IPM) was synthesized with isotopic enrichment at oxygen. Labelled benzaldehyde was made by exchange with isotopically enriched water (13.4 atom % 170, 25.5 atom % 180) and this was then reduced with sodium borohydride to give labelled benzyl alcohol (72% yield). Triethylamine and labelled benzyl alcohol were added to POCl3/CHCl3 at −23°C. Subsequent addition of 2‐chloroethylamine hydrochloride (2 equiv) and then triethylamine (4.4 equiv) (−15°C) provided 170/180 enriched N,N′‐bs‐(2‐chloroethyl)phosphorodiamidic acid phenylmethyl ester [61%, BzOP(O)(NHCH2CH2Cl)2]. Catalytic (10% Pd/C) hydrogenation of this ester at atmospheric pressure gave IPM (22%). GC/MS was used to determine mole percent enrichments of 9.3% 170 and 17.9% 180 for IPM (single labelling within one molecule).
Synthesis and purification of desmethylzopiclone‐N‐{3‐(4‐hydroxy‐3‐[125I]‐iodophenyl) propionamide}, a prosthetic derivative of zopiclone for use in immunoassay
Authors: Mannaert E. , Daenens P.
Published: October 2006

Condensation of [125I]‐Bolton/Hunter reagent with N‐desmethylzopiclone lead to the title compound which was isolated and purified by normal phase HPLC, in combination with gamma counting detection. The introduction of the prosthetic group into the tracer precursor was proven by L‐SIMS.
A facile synthesis of pentadeuterated domiodol (2‐iodomethyl‐4‐hydroxymethyl‐1,3‐dioxolane) from glycerol‐1,1,2,3,3‐d5
Authors: Ferraboschi Patrizia , Grisenti Paride , Santanitllo Enzo
Published: October 2006

The acid catalyzed reaction of glycerol‐d5 with bromoacetaldehyde dimethyl acetal affords the corresponding 2‐bromomethyl‐4‐hydroxymethyl‐1,3‐dioxolane, which was treated with lithium iodide in 2‐butanone to afford the pentadeuterated domiodol 1 in high isotopic purity.
The synthesis of some tritium‐labelled terminators of DNA synthesis
Authors: Sidorov Georgy V. , Myasoedov Nykolai F. , Yasko Maxim V.
Published: October 2006

2′,3′‐Dideoxythymidine, 2′,3′‐dideoxyadenosine, 2′,3′‐dideoxycytidine‐5′‐phosphonate, thymidine‐5′‐phosphonate, labelled with tritium in the carbohydrate residue; thymidine‐5′‐methylphosphonate labelled in the methyl of the phosphonate group and 2′,3′‐dideoxyadenosine labelled in the base and/or carbohydrate residue were prepared by hydrogenolysis with tritium gas. The reaction of solid state catalytic hydrogenation was studied and tritium‐labelled azydothymidine, azydothymidine‐5′‐phosphonate, acyclovire, acyclovire‐5′‐phosphonate were synthesized. A number of general approaches to the synthesis of tritium‐labelled terminators of DNA synthesis were formulated.
The solid‐state synthesis of tritium labelled heterocyclic bases
Authors: Sidorov Georgy V. , Myasoedov Nikolai F.
Published: October 2006

The results of a study of. the solid‐state catalytic hydrogenation and the synthesis of tritium labelled native heterocyclic bases are presented. The effect of different palladium catalysts and reaction conditions on yield and molar radioactivity of final compounds was investigated. For some compounds, data on the intramolecular distribution of tritium were obtained by using the isotope exchange reaction and tritium NMR. Tritium labelled purine and pyrimidine bases (25–180 Ci/mmol.) were synthesized.
Synthesis of the 14C‐labelled juvenoid W328
Authors: Elbert Tomas , Havlicek Libor , Wimmer Zdenek , Bubner Marianne
Published: October 2006

The labelled juvenoid 2‐(4‐(2‐(ethoxycarbamatoethoxy)(benzene‐U‐14C)benzyl) ‐1‐cyclohexanone ethylene acetal (8) (W 328) was prepared starting from p‐hydroxy(ring‐U‐14C)benzoic acid (1) by a seven step synthesis in 11% overall yield. The reaction conditions previousiy reported for the „coid”︁ synthesis of the W 328 (8) were modified to suit the small scale preparation.
Radiolabelling optimization of 5‐(4‐[125I]‐iodophenyl)‐2,3 dihydro‐5‐hydroxy‐5H‐imidazo[2,1‐a]isoindole or [125I]‐iodo mazindol : A potential tool for spect explorations
Authors: Galinier E. , Ombetta J. E. , Frangin Y. , Mertens J. , Besnard J. C. , Guilloteau D.
Published: October 2006

The radiolabelling of an iodinated analog of mazindol, 5‐(4‐[125I]‐iodophenyl)‐2,3‐dihydro‐5‐hydroxy‐5H‐imidazo[2,1‐a]isoindole, was performed in order to develop a potential tool for SPECT exploration of the presynaptic dopamine transporter in the human brain. Radiosynthesis was performed by iodide for bromide nucleophilic exchange from a brominated precursor. The reaction was carried out in the presence of the copper I catalyst and reducing and complexing agents. In these radiolabelling conditions, [125I] iodomazindol exhibited a tautomeric equilibrium. Therefore, in order to obtain the best labelling conditions, we studied variables such as copper I catalyst and brominated precursor concentrations, reaction temperature and heating time involved in the reaction.

This study of the kinetics could be used as a pattern for the radiosynthesis of other compounds which can be present in a tautomeric equilibrium under particular conditions. Indeed, we describe a convenient procedure to obtain each tautomeric form with high radiochemical purity in optimum radiolabelling conditions.
Stereoselective synthesis of 3‐o‐methyl‐6‐[18F]fluorodopa via fluorodestannylation
Authors: Adam Michael J. , Lu Jianming , Jivan Salma
Published: October 2006

3‐O‐Methyl‐6‐[18F]fluorodopa was synthesized in 20% radiochemical yield in 60 min, with a specific activity of 500 mCi/mmol, by the fluorination of a stannylated dopa precursor with [18F]‐acetyl hypofluorite.
Simple synthesis of multiply labelled sodium propionate
Authors: Iida Katsumi , Uegaki Ryuichi , Kajiwara Masahiro
Published: October 2006

Sodium [3‐13C]‐ and [3‐13CD3]propionate were conveniently synthesized from 2,4,4‐trimethyl‐2‐oxazoline. The numbers and locations of deuterium labels were confirmed by broad‐band deuterium and proton‐decoupled 13C‐nuclear magnetic resonance (13C‐{1H} {D}NMR) spectroscopy and fast atom bombardment mass (FAB‐MS) spectroscopy.
Synthesis of 2H, 3H and 14C labelled Sch 40120
Authors: Hesk D. , Duelfer T. , Hickey S. , Hochman D. , Koharski D. , McNamara P. , Saluja S.
Published: October 2006

2H and 3H labelled Sch 40120 were prepared by Pt catalysed exchange with isotopic water. D7‐Sch 40120 was obtained in two exchanges in 53% yield and 3H‐Sch 40120 was prepared by a single exchange at a specific activity of 19.8 Ci/mmole. 14C‐Sch 40120 was prepared in 4 steps from 14C‐m‐chloro aniline in overall 16% radiochemical yield.
Tritiation of organic compounds by polymer‐supported base catalysts
Authors: Brewer J. R. , Jones J. R. , Lawrie K. W. M. , Saunders D. , Simmonds A.
Published: October 2006

A range of organic compounds have been tritiated (and in some cases deuteriated) via hydrogen isotope exchange reactions using polymer supported base catalysts. The problem of poor thermal stability of some commercially available anion exchange resins, which limits their use as tritiation catalysts, has been overcome by the preparation of a more stable polymer supported pyridinium salt. The anion exchange resins are as effective at very high activities of tritiated water as they are at low and compounds containing nitro groups, which poison metal‐catalysed exchange reactions, can be successfully labelled.
Labelling of brefeldin‐a by catalyzed isotopic exchange with tritium gas
Authors: Maetz Ph. , Sobrio F. , Mioskowski C. , Rousseau B.
Published: October 2006

The hydrogen isotope exchange of Brefeldin‐A with tritium gas (T2) in 1,4‐dioxane was studied over a commercial palladium catalyst supported on diatomaceous earth (5% metallic weight). The effect of the gas phase was studied. Addition of air in the gas phase led to an increase of the catalytic activity. Moreover, exchange was enhanced when the air/T2 ratio reached a value of 4. This latter result is interpreted, principally, in terms of a strongly poisoning of the metallic particles together with an effect of the T2 partial pressure. Through the comparison with Pd(II) oxide, the role of the support is also shown. The specific activities ranged up to 2.8 Ci/mMoles. The labelled product was analyzed by 3H NMR. Possible mechanisms for tritium incorporation are discussed and two different adsorbed species, on the catalyst surface, are involved.
A novel synthesis of carbon‐labelled quinolone‐3‐carboxylic acid antibacterials
Authors: Carr Richard M. , Sutherland Derek R.
Published: October 2006

3‐lodoquinolones were prepared from the corresponding quinolone‐3‐carboxylic acids by Hunsdiecker‐type iododecarboxylation reactions with lead tetraacetate and iodine. Cyanation of the iodo compounds with mixtures of potassium [13C]cyanide and copper (I) iodide, gave [3‐13C]cyanoquinolones which on acidic hydrolysis afforded quinolone‐[3‐13C]carboxylic acids. In this way, nalidixic acid, an immediate precursor of norfloxacin, and quinolone WIN57273 were labelled with carbon‐13 in the metabolically stable carboxylic acid fragment.
Synthesis and stability of [1,3‐14C2]‐glyceryl trinitrate
Authors: Szammer J. , Simon‐Trompler E. , Máté J. , Abermann M. , Klebovich I.
Published: October 2006

The synthesis of [1,3‐14C2]‐glyceryl trinitrate (14C]‐GTN) labelled with quasi carrier free carbon‐14 atom in the 1,3‐positions of the molecule was effected in four reaction steps from 14CO2 (3,5 % overall yield). The chemical and radiochemical purity of [14C]‐GTN was found better than 99% controlled by HPLC‐Radioactivity Monitor and TLC‐Digital Autoradiograph methods. Study of the radiochemical stability in dilute solution at 5 °C shows that the product can be stored at least for a month without detectable decomposition.
Preparation of [3H]‐labelled benzphetamine photoaffinity probes for cytochrome P‐450
Authors: Hodek Petr , Strobel Henry W.
Published: October 2006

We have synthesized two tritium labelled photolabile azid‐α‐desmethylbenzphetamine analogues: N‐benzyl‐N‐methyl‐p‐azido‐phenethylamine ([3H]BP‐N3) and N‐(p‐azidobenzyl)‐N‐methyl‐p‐azido‐phenethylamine ([3H]N3‐BP‐N3). These compounds, photoaffinity probes for cytochrome P450 2B1, were prepared in a two step synthetic process. First, the iodinated aminoderivative precursors N‐benzyl‐N‐methyl‐4‐amino‐3,5‐diiodophenethylamine and N‐(4‐amino‐3,5‐diiodobenzyl)‐N‐methyl‐4‐amino‐3,5‐diiodophenethylamine were subjected to reductive deiodination on a Pd/C catalyst using sodium [3H]borohydride as an in situ generator of tritium gas. Second, resultant radiolabelled amino‐compounds were converted into the final [3H]BP‐N3 and [3H]N3‐BP‐N3 compound through their diazoderivatives without separation of their intermediates.
Preparation of 18O‐labelled m‐chloroperbenzoic acid
Authors: Jankowski Stefan , Kamiński Rafat
Published: October 2006

A method for the preparation of 18O‐labelled m‐chloroperbenzoic acid (MCPBA) from H2 18O2 is described.
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

N‐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

A 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

In 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

(−)‐[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

2′‐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

Using 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

Emodin, 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

N‐(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

2H 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

The 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

The 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

[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

C‐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

An 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

A 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

The 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

4‐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

The 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

Bei 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

The 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

A 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

A 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.
Labelled compounds : The user and the supplier
Authors: Catch John R.
Published: October 2006

The uses of radioactive research chemicals are too diversified to permit of detailed standardisation and specification. The best safeguards for the user are a full description by the supplier, a careful study of the supplier's evidence by the user, and good communication between both.
Recent developments in the chromatographic analysis and purification of radioactively laeelled lipids
Authors: Mukherjee K. D. , Mangold H. K.
Published: October 2006

Methods 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.
Rapid Volume Verification in High-Density Microtiter Plates Using Dual-Dye Photometry
Authors: Knaide Tanya R. , Bradshaw John Thomas , Rogers Alex , McNally Ceara , Curtis Richard H. , Spaulding Benjamin W.
Published: October 2006

The dual-dye photometric technology used by Artel's Multichannel Verification System (MVS) overcomes challenges associated with determining the dispensed volume within each well of a 384-well microtiter plate. The MVS volume measurement approach (Bradshaw, J. T.; Knaide, T.; Rogers, A.; Curtis, R. Multichannel verification system (MVS): a dual dye ratiometric photometry system for performance verification of multichannel liquid delivery devices. Journal of the Association for Laboratory Automation 2005, 10, 35–42) has been extended to 384-well plates and volumes as low as 30 nL. The measurements collected by the MVS in less than 15 min provide both precision and accuracy values per individual channel. The system capabilities enable easy optimization of small-volume dispense protocols to minimize waste of valuable samples.
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.
A Leiomyoma Arising From the Deep Palmar Arterial Arch
Authors: YAGI K. , HAMADA Y. , YASUI N.
Published: October 2006

Vascular leiomyomas, or angioleiomyomas, are benign tumours originating from smooth non-striated muscle. Leiomyomas in the hand are uncommon and their pre-operative diagnosis is difficult. We report a 65 year-old woman who developed a vascular leiomyoma arising from the deep palmar arterial arch.
Semantic Processing Precedes Affect Retrieval: The Neurological Case for Cognitive Primacy in Visual Processing
Authors: Storbeck Justin , Robinson Michael D. , McCourt Mark E.
Published: October 2006

According to the affective primacy hypothesis, visual stimuli can be evaluated prior to and independent of object identification and semantic analysis (Zajonc, 1980, 2000 ). Our review concludes that the affective primacy hypothesis is, from the available evidence, not likely correct. Although people can react to objects that they cannot consciously identify, such affective reactions are dependent upon prior semantic analysis within the visual cortex. The authors propose that the features of objects must first be integrated, and then the objects themselves must be categorized and identified, all prior to affective analysis. Additionally, the authors offer a preliminary neurological analysis of the mere exposure and affective priming effects that is consistent with the claim that semantic analysis is needed to elicit these effects. In sum, the authors conclude that the brain must know what something is in order to know whether it is good or bad.
Inherent limitations in protein–protein docking procedures
Authors: Kowalsman Noga , Eisenstein Miriam
Published: October 2006

Motivation: 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 website

Contact:  

Supplementary information: Supplementary data are available at Bioinformatics online.