bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unusual extended fibular origin of the human soleus muscle: Possible morpho‐physiologic significance based on comparative anatomy
Authors: Barberini F. , Bucciarelli‐Ducci C. , Zani A. , Cerasoli D. 
Published: August 2003

AbstractA bilateral anomalous extended origin of the soleus muscle was observed in a 73‐year‐old female cadaver. It arose from the head, neck, and proximal two‐thirds of the medial crest of the fibula and ran through the posterior intermuscular septum of the leg, from the lateral border of the fibula. The soleus muscle formed the vault of a muscular tunnel, overcoming the deep flexor muscles of the leg that was about 15 cm in length and directed inferiorly and laterally. The extended fibular origin delimited a blind recess lateral to the muscular tunnel and parallel to the posterior surface of the fibula. This recess measured 6.5 cm in length and extended 3.5 cm above the inferior opening of the muscular tunnel; the superior portion of the flexor hallucis longus was housed within it between the portions of the extended origin from the medial crest of the fibula and posterior intermuscular septum. The neurovascular bundle of the posterior leg coursed in the muscular tunnel. The tibial origin and calcaneal insertion of the soleus muscle were normal. Phylogenetic studies of the muscles of the lower limbs in mammals indicate that the fibular origin of soleus is more constant than the tibial origin and, in primates, the fibular origin is the only one observed in most monkeys. The case reported might be considered a conspicuous enlargement of the fibular origin observed in primates. This large fibular origin of the soleus muscle may prove to be a difficulty during surgery when accessing the proximal two‐thirds of the fibula for ligation of the peroneal artery. Clin. Anat. 16:383–388, 2003. © 2003 Wiley‐Liss, Inc.
Branches of the splenic artery and splenic arterial segments
Authors: Daisy Sahni A. , Indar Jit B. , Gupta C.N.M. , Gupta D. Madhur , Harjeet E. 
Published: August 2003

AbstractIn 200 adult autopsy specimens, the arterial supply to the pancreas and spleen was studied radiologically and by manual dissection. The splenic artery divided into two or three lobar arteries, which supplied its corresponding lobe; each lobar artery subsequently divided into two to four lobular branches. Six to twelve lobular branches were observed entering the splenic substance at the hilum. Lobar arteries did not anastomose with each other, hence, the lobes of the spleen are also termed segments. The lobules, however, were not found to be independent segments and the arteries of one lobule anastomosed with those of other lobules. The branching pattern of the splenic artery varied from one specimen to another, so much so that a prevailing pattern could not be identified. Polar arteries, particularly to the superior pole, arose quite proximal to the hilum in 51% of cases and were occasionally missed. In 45% of males and 40% of females, the posterior gastric artery arose from about the middle of the splenic artery. The splenic artery was not found to be tortuous in fetuses, newborns, and young children. Tortuosity was seen in only 10% of adults; thus, the characteristic tortuosity of the splenic artery appears to develop with age. Clin. Anat. 16:371–377, 2003. © 2003 Wiley‐Liss, Inc.
Alteration of the Substrate Specificity of Benzoylformate Decarboxylase from Pseudomonas putida by Directed Evolution
Authors: Lingen Bettina , Kolter‐Jung Doris , Dünkelmann Pascal , Feldmann Ralf , Grötzinger Joachim , Pohl Martina , Müller Michael 
Published: July 2003

AbstractAlteration of the substrate specificity of thiamin diphosphate (ThDP)‐dependent benzoylformate decarboxylase (BFD) by error‐prone PCR is described. Two mutant enzymes, L476Q and M365L‐L461S, were identified that accept ortho‐substituted benzaldehyde derivatives as donor substrates, which leads to the formation of 2‐hydroxy ketones. Both variants, L476Q and M365L‐L461S, selectively catalyze the formation of enantiopure (S)‐2‐hydroxy‐1‐(2‐methylphenyl)propan‐1‐one with excellent yields, a reaction which is only poorly catalyzed by the wild‐type enzyme. Different ortho‐substituted benzaldehyde derivatives, such as 2‐chloro‐, 2‐methoxy‐, or 2‐bromobenzaldehyde are accepted as donor substrates by both BFD variants as well and conversion with acetaldehyde resulted in the corresponding (S)‐2‐hydroxy‐1‐phenylpropan‐1‐one derivatives. As deduced from modeling studies based on the 3D structure of wild‐type BFD, reduction of the side chain size at position L461 probably results in an enlarged substrate binding site and facilitates the initial binding of ortho‐substituted benzaldehyde derivatives to the cofactor ThDP.
Structural Investigation of the HIV‐1 Envelope Glycoprotein gp160 Cleavage Site, 2: Relevance of an N‐Terminal Helix
Authors: Oliva Romina , Falcigno Lucia , D′Auria Gabriella , Dettin Monica , Scarinci Claudia , Pasquato Antonella , Di Bello Carlo , Paolillo Livio 
Published: July 2003

AbstractProteolytic activation of the HIV‐1 envelope glycoprotein gp160 is selectively performed by the proprotein convertase furin at the C‐terminus of the sequence R508–E–K–R511 (site 1), in spite of the presence of another consensus sequence, Lys500–Ala–Lys–Arg503 (site 2). On the basis of the solution structural analysis of the synthetic peptide p498, spanning the gp160 sequence Pro498–Gly516, we previously suggested a possible role of an N‐terminal helix in regulating the exposure and accessibility of the gp160 physiological cleavage site, enclosed in a loop. Here we report on the activity and conformation of the 23‐residue peptide h‐REKR, designed to exhibit a large N‐terminal helix, followed by the gp160 native sequence, Arg508–Gly516. h‐REKR is digested by furin with high efficiency, comparable to the full native p498. Circular dichroism analyses, in mixtures from pure water to 98 % trifluoroethanol, outline a significant content of helical structure in the peptide conformation. The molecular model obtained from NMR data collected in trifluoroethanol/water, by means of DYANA and AMBER simulations, indeed has helical structure on a large N‐terminal segment. Such a long helix does not seem to affect the loop conformation of the C‐terminal site 1‐containing sequence, which exhibits the same proton chemical shifts already observed for the full native p498.
Tamoxifen Derivatives for Delivery of the Antitumoral (DACH)Pt Group: Selective Synthesis by McMurry Coupling, and Biochemical Behaviour
Authors: Top Siden , Kaloun El Bachir , Vessières Anne , Leclercq Guy , Laïos Ioanna , Ourevitch Michèle , Deuschel Christine , McGlinchey Michael J. , Jaouen Gérard 
Published: July 2003

AbstractThe goal of our study was to potentiate the effects of the ((R,R)‐trans‐1,2‐diaminocyclohexane)‐platinum(II) fragment [(DACH)Pt], known for its cytotoxic properties, either with tamoxifen (Tam), the most widely used antiestrogen in the treatment of hormone‐dependent breast cancers, or with its active metabolite hydroxytamoxifen (hydroxy‐Tam). We coupled Tam or hydroxy‐Tam derivatives bearing a malonato group at the para position of the β aromatic ring with the (DACH)Pt fragment. The malonato‐Tam and malonato‐hydroxy‐Tam compounds were prepared through McMurry coupling of the appropriate ketones. The presence of the malonate group resulted in a pronounced stereospecificity in the reaction, since malonato‐Tam was obtained only as the Z isomer, while malonato‐hydroxy‐Tam was obtained as an 80/20 E/Z mixture. Attribution of the isomeric structures was achieved by 2D NMR spectroscopy. The platinum complexes (DACH)Pt‐malonato‐Tam and (DACH)Pt‐malonato‐hydroxy‐Tam were then prepared by coupling the barium salts derived from the malonato‐Tam and malonato‐hydroxy‐Tam with the nitrate derived from (DACH)PtCl2. Study of the biochemical properties of these two platinum complexes showed that, while the hydroxy‐Tam complex is satisfactorily recognized by the estrogen receptor (relative binding affinity, RBA=6.4 %), the Tam complex is less well recognized (RBA=0.5 %). The effects of these complexes on two hormone‐dependent breast cancer cell lines (MCF7 and MVLN) were studied in vitro. Both complexes showed an antiproliferative effect on MCF7 cells, and an antiestrogenic effect on MVLN cells. The observed effects appear to be essentially antihormonal, since incorporation of the (DACH)Pt fragment into the tamoxifen skeleton did not cause an increase in the cytotoxicity of the complexes.
Photoreversible Inhibition of Cholinesterases: Catalytic Serine‐Labeled Caged Butyrylcholinesterase
Authors: Loudwig Sandra , Nicolet Yvain , Masson Patrick , Fontecilla‐Camps Juan C. , Bon Suzanne , Nachon Florian , Goeldner Maurice 
Published: July 2003

AbstractThe photoregulation of the catalytic activity of butyrylcholinesterase (BChE) was investigated by treating the enzyme with a newly developed carbamylating reagent, N‐methyl‐N‐(2‐nitrophenyl)carbamoyl chloride, which has proved to be an efficient photoremovable alcohol‐protecting group. BChE was efficiently inhibited in a time‐ and concentration‐dependent manner, and the enzyme could be protected against inhibition by active‐site‐specific ligands (that is, tacrine). The inactivation kinetics showed a biphasic character, which can be analyzed as the result of the existence of two conformational states in solution. Pseudo‐irreversible inactivation of BChE, which results from catalytic serine carbamylation, was suggested by recovery of the enzyme activity after dilution and was demonstrated by X‐ray crystallography. Remarkably, the 3D structure of the carbamylated BChE conjugate showed a nonambiguous carbamylation of the catalytic serine residue as the only chemical modification on the protein. The photoreversibility of the enzyme inactivation was analyzed by irradiating the inactivated enzyme at 365 nm and was shown to reach completion in some conditions. The efficient and specific “caging” of BChE, together with the availability of carbamylated BChE crystals, will offer a unique possibility to study the catalytic properties of this enzyme by kinetic crystallography after cryophotolytic uncaging of the enzyme conjugate crystals.
Protein Stabilisation by Compatible Solutes: Effect of Mannosylglycerate on Unfolding Thermodynamics and Activity of Ribonuclease A
Authors: Faria Tiago Q. , Knapp Stefan , Ladenstein Rudolf , Maçanita António L. , Santos Helena 
Published: July 2003

AbstractDifferential scanning calorimetry, optical spectroscopy, and activity measurements were used to investigate the effect of mannosylglycerate, a negatively charged osmolyte widely distributed among thermophilic and hyperthermophilic archaea and bacteria, on the thermal unfolding of ribonuclease A (RNase A). For comparison, assays in the presence of trehalose, a canonical solute in mesophiles, and potassium chloride were also carried out. A thermodynamic analysis was performed by using differential scanning calorimetry data. The changes in the heat capacity for unfolding were similar for the different solutes examined. Mannosylglycerate was an efficient thermostabiliser of RNase A and induced an increase of 6 °C mole‐1 in the melting temperature. Moreover, the performance of mannosylglycerate as a stabiliser depended on the net charge of the molecule, with the maximal effect being observed at pH values above 4.5. Analysis of the enthalpic and entropic contributions to unfolding, derived from calorimetric data, revealed that the stabilisation rendered by mannosylglycerate is primarily achieved through a decrease in the unfolding entropy. Also, the number of protons taken up by RNase A upon denaturation in the presence of mannosylglycerate was considerably higher than with other solutes, a result consistent with a more rigid structure of the native protein. Mannosylglycerate (potassium salt) inhibited the activity of RNase A, albeit to a smaller extent than KCl, and acted as an efficient suppressor of aggregation of the denatured protein, thereby having a remarkable beneficial effect on the inactivation of RNase A upon thermal denaturation. The results are discussed in view of the physiological role of this charged compatible solute.
Comparative Study of Purine and Pyrimidine Nucleoside Analogues Acting on the Thymidylate Kinases of Mycobacterium tuberculosis and of Humans
Authors: Pochet Sylvie , Dugué Laurence , Labesse Gilles , Delepierre Muriel , Munier‐Lehmann Hélène 
Published: July 2003

AbstractThymidine monophosphate kinase (TMPK) from Mycobacterium tuberculosis (TMPKmt) is an attractive target for the design of specific inhibitors. This fact is the result of its key role in the thymidine pathway and of unique structural features in the active site observed by X‐ray crystallography, especially in comparison to its human counterpart (TMPKh). Different 5‐modified thymidine derivatives, as well as purine and pyrimidine analogues or C‐nucleosides were tested on TMPKmt and TMPKh, and the results were rationalized by docking studies. 5‐Halogenated 2′‐deoxyuridines are the best inhibitors of TMPKmt found and present the highest selectivity indexes in favor of TMPKmt.
CloN6, a Novel Methyltransferase Catalysing the Methylation of the Pyrrole‐2‐carboxyl Moiety of Clorobiocin
Authors: Westrich Lucia , Heide Lutz , Li Shu‐Ming 
Published: July 2003

AbstractThe aminocoumarin antibiotic clorobiocin contains a 5‐methylpyrrole‐2‐carboxylic acid unit. This pyrrole unit is derived from L‐proline, and it would be expected that its 5‐methyl group should be introduced by a methylation reaction. However, sequence analysis of the clorobiocin biosynthetic gene cluster did not reveal a gene with sequence similarity to the SAM‐dependent methyltransferases that could be assigned to this reaction. This study, however, has provided evidence that the gene cloN6 is involved in this methylation reaction. Its gene product CloN6 shares conserved sequence motifs with the recently identified radical SAM protein superfamily, and it has been suggested that members of this family can catalyse methylcobalamin‐dependent methylation reactions. cloN6 was inactivated in the clorobiocin producer Streptomyces roseochromogenes var. oscitans DS 12.976 by use of the PCR‐targeting method. The cloN6− mutants accumulated, instead of clorobiocin, a derivative lacking the 5′′′‐methyl group of the pyrrole moiety (termed novclobiocin 109). A structural isomer carrying the pyrrole‐2‐carboxyl moiety at 2″‐OH rather than at the 3″‐OH of the deoxysugar (novclobiocin 110), and a derivative completely lacking the pyrrole unit (novclobiocin 104) were also identified. The structures of the metabolites were confirmed by NMR and MS analysis. Antibacterial activity tests against Bacillus subtilis showed that novclobiocin 109 and novclobiocin 110 have antibacterial activities about eight times less than that of clorobiocin, whereas novclobiocin 104 showed no activity under the test conditions.
Selection of D‐Amino‐Acid Peptides That Bind to Alzheimer's Disease Amyloid Peptide Aβ1–42 by Mirror Image Phage Display
Authors: Wiesehan Katja , Buder Katrin , Linke Reinhold P. , Patt Stephan , Stoldt Matthias , Unger Eberhard , Schmitt Bettina , Bucci Enrico , Willbold Dieter 
Published: July 2003

AbstractA mirror image phage display approach was used to identify novel and highly specific ligands for Alzheimer's disease amyloid peptide Aβ(1–42). A randomized 12‐mer peptide library presented on M13 phages was screened for peptides with binding affinity for the mirror image of Aβ(1–42). After four rounds of selection and amplification the peptides were enriched with a dominating consensus sequence. The mirror image of the most representative peptide (D‐pep) was shown to bind Aβ(1–42) with a dissociation constant in the submicromolar range. Furthermore, in brain tissue sections derived from patients that suffered from Alzheimer's disease, amyloid plaques and leptomeningeal vessels containing Aβ amyloid were stained specifically with a fluorescence‐labeled derivative of D‐pep. Fibrillar deposits derived from other amyloidosis were not labeled by D‐pep. Possible applications of this novel and highly specific Aβ ligand in diagnosis and therapy of Alzheimer's disease are discussed.
Cover Picture: Direct Visualization of DNA Duplex Formation on the Surface of a Giant Liposome (ChemBioChem 8/2003)
Authors: Shohda Koh‐ichiroh , Toyota Taro , Yomo Tetsuya , Sugawara Tadashi 
Published: July 2003

AbstractThe cover picture shows the phase‐contrast microscopy image (top left) and the fluorescent microscopy image (bottom left) of a giant liposome stained with a green fluorescent probe on the surface of the membrane (right diagram). This process occurs by hybridization of a fluorescent‐tagged DNA 15mer (green) and a conjugate DNA molecule, the latter of which is composed of a DNA 15mer (orange ribbon), a polyethyleneglycol spacer (orange ball), and cholesterol (orange rugby ball). Since the conjugate molecule is firmly anchored to the membrane of the giant liposome, it will become a bridging molecule between the world of RNA and lipids. Further details can be found in the article by T. Sugawara et al. on p. 778 ff.
The First Successful Crystallographic Characterization of a Cyclodextrin Dimer: Efficient Synthesis and Molecular Geometry of a Doubly Sulfur‐Bridgedβ‐Cyclodextrin
Authors: Yuan De‐Qi , Immel Stefan , Koga Katzutaka , Yamaguchi Masatoshi , Fujita Kahee 
Published: July 2003

Abstractβ‐Cyclodextrin is transannularly disulfonylated at the 6A‐ and 6B‐positions, and then converted to the corresponding 6A,6B‐diiodide and 6A,6B‐dithiol. Cross‐coupling of the latter two species yields a single head‐to‐head‐coupledβ‐cyclodextrin dimer5with two sulfur linkers at adjacent 6‐methylene carbons. NMR and X‐ray analysis revealed thetrans‐type (“aversive”) linkage of bothβ‐cyclodextrin units. In the solid‐state structure of5⋅5 MeOH⋅23 H2O, the undistorted cyclodextrin macrocycles feature almost parallel ring planes pointing away from each other, leaving5with a “handcuff‐like” appearance of approximateC2symmetry. This work represents the first successful crystallographic study on a cyclodextrin dimer.
Tuning the Redox Potentials of Dinuclear Tungsten Oxo Complexes [(Cp*W(4,4′‐R,R‐2,2′‐bpy)(μ‐O))2][PF6]2 Toward Photochemical Water Splitting
Authors: Cremer Christian , Burger Peter 
Published: July 2003

AbstractA series of novel dinuclear tungsten(IV) oxo complexes with disubstituted 4,4′‐R,R‐2,2′‐bipyridyl (R2bpy) ligands of the type [(Cp*W(R2bpy)(μ‐O))2][PF6]2 (R=NMe2, tBu, Me, H, Cl) was prepared by hydrolysis of the tungsten(IV) trichloro complexes [Cp*W(R2bpy)Cl3]. Cyclic voltammetry measurements for the tungsten(IV) oxo compounds provided evidence for one reversible oxidation and two reversible reductions leading to the oxidation states WVWIV, WIVWIII and WIIIWIII. The corresponding complexes [(Cp*W(R2bpy)(μ‐O))2]n+ [PF6]n (n=0 for R=Me, tBu, and 1, 3 for both R=Me) could be isolated after chemical oxidation/reduction of the tungsten(IV) oxo complexes. The crystal structures of the complexes [(Cp*W(R2bpy)(μ‐O))2][BPh4]2 (R=NMe2, tBu) and [(Cp*W(Me2bpy)(μ‐O))2]n+[PF6]n (n=0, 1, 2, 3) show a cis geometry with a puckered W2O2 four‐membered ring for all compounds except [(Cp*W(Me2bpy)(μ‐O))2] which displays a trans geometry with a planar W2O2 ring. Examining the interaction of these novel tungsten oxo complexes with protons, we were able to show that the WIVWIV complexes [(Cp*W(R2bpy)(μ‐O))2][PF6−]2 (R=NMe2, tBu) undergo reversible protonation, while the WIIIWIII complexes [(Cp*W(R2bpy)(μ‐O))2] transfer two electrons forming the WIVWIV complex and molecular hydrogen.
Synthesis of a New Potential Tridentate Anthracene Ligand Bearing Deprotectable Methoxymethoxy (OMOM) Group at 1,8‐Positions: Attempt To Synthesize Anionic Hypervalent Carbon Compounds
Authors: Yamashita Makoto , Mita Yukari , Yamamoto Yohsuke , Akiba Kin‐ya 
Published: July 2003

AbstractA novel potential tridentate ligand bearing deprotectable coordinating atoms, 1,8‐bis(methoxymethoxy)‐9‐bromoanthracene (15), was synthesized. The key steps are as follows: 1) stepwise mono‐oxygenation from 1,8‐dibromo‐9‐methoxyanthracene by use of electrophilic oxaziridine and gaseous dioxygen, and 2) selective reduction of the methoxy group by LDBB (lithium di‐tert‐butylbiphenylide) followed by treatment with BrCF2CF2Br. The corresponding 1,8‐bis(methoxymethoxy)‐9‐lithio‐anthracene (14), which should be a useful versatile trianion equivalent, could be generated by treatment of the bromide with one equivalent of nBuLi. The lithioanthracene reacted with hexafluoroacetone to give the deprotected ether 17 together with the adduct alcohol 16. The ether could easily be deprotected to give 1,2‐dihydro‐1,1‐bis(trifluoromethyl)‐2‐oxa‐9‐hydroxyanthrylene (8), which was deprotonated with KH in the presence of [18]crown‐6 to give the corresponding anion (9‐K([18]crown‐6)). The X‐ray structure and NMR spectra of 9‐K([18]crown‐6) showed that it has an unsymmetrical structure probably due to the interaction between the oxygen atom of the phenoxide and the potassium cation surrounded by the crown ether.
On the Electronic Structures of the 1,3‐Diboracyclobutane‐1,3‐diyls and Their Valence Isomers with a B2E2 Skeleton (E=N, P, As)
Authors: Schoeller Wolfgang W. , Rozhenko Alexander , Bourissou Didier , Bertrand Guy 
Published: July 2003

AbstractThe concept of through‐space versus through‐bond interactions on the stabilization of biradical structures with a singlet or triplet ground state is evaluated for the 1,3‐diboracyclobutane‐1,3‐diyls and related congeners. Singlet biradicals are favored when the intermediate units E feature singlet character (PH2+, AsH2+), while E fragments with triplet character (NH2+) induce small energy separations between the lowest singlet and triplet states. These considerations are supported by quantum chemical calculations with energy optimization at 1) MCSCF level plus MR‐MP2 correction, 2) MR‐MP2 level, and 3) two different types of density functional levels for the planar (D2h) geometries. The singlet–triplet energy separations in the planar compounds increase with increasing singlet stability of the corresponding E fragments. In addition to this newly developed principal features for singlet stabilization, which primarily occurs in bonded structures with higher main‐group elements, the corresponding valence isomers with bicyclobutane, cyclobutene and cis‐butadiene structures are investigated.