bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the structural parameters involved in the δ‐opioid selectivity of several families of opioid peptides
Authors: GUIS CHRISTINE , BRUETSCHY LUCE , MEUDAL HERVÉ , ROQUES BERNARD P. , GACEL GILLES A. 
Published: August 2010

Three series of highly δ‐opioid selective peptides are now available, and each family is used as template to investigate the structural parameters involved in δ‐receptor recognition and in the modulation of the selectivity of the parent peptide. The first series includes cyclic derivatives such as Tyr‐D‐Pen‐Gly‐Phe‐D‐Pen(DPDPE) and Tyr‐D‐Pen‐Gly‐Phe‐Pen(DPLPE); the second are the synthetic linear constrained peptides [Tyr‐D‐Ser(OtBu)‐Gly‐Phe‐Leu‐Thr(DSTBULET), Tyr‐D‐Ser(OtBu)‐Gly‐Phe‐Leu‐Thr(OtBu) (BUBU) and especially Tyr‐D‐Cys(StBu)‐Gly‐Phe‐Leu‐Thr(OtBu) (BUBUC)] and the last one the natural peptides [Tyr‐D‐Met‐Phe‐His‐Leu‐Met‐Asp‐NH2(deltorphin or dermenkephalin) and Tyr‐D‐Ala‐Phe‐Asp‐Val‐Val‐GlyNH2([D‐Ala2] deltorphin I)].In the present study, the possibly of transposing some of the decisive factors of δ‐selectivity evidenced in the two other families, to the linear constrained peptides series was examinated. With this aim in view, residues such as Phe3, pClPhe4or Asp were introduced in the sequence of DSTBULET, BUBU or BUBUC.Direct comparison between the biochemical profiles of the [pClPhe4] analogs of the linear constrained peptides and their parent compounds shows that the addition of an electronegative atom on the Phe4residue of enkephalin sequences is not an absolute parameter for δ‐selectivity improvement. The hydrophobic δ‐receptor subsite seems able to receive a range of molecular volumes and electronegativities. By contrast, this subsite cannot interact with a Phe3aromatic ring introduced in this series of peptides. Moreover, the results obtained with linear peptides including additional negatively charged residues demonstrate that the proposed location of the δ‐receptors in a cationic membrane environment is not adequate to explain the selectivity profile of a number of compounds.
Solution structure of the toxic octapeptide, lophyrotomin
Authors: DALY NORELLE L. , ATKINS ANNETTE R. , SMITH ROSS 
Published: August 2010

Lophyrotomin is a toxic octapeptide, first isolated from larvae of the sawfly Lophyrotoma interrupta, which causes the death of cattle and sheep. It appears to act principally‐ on the liver, however very little is known about the cellular site and mechanism of action. In the present study lophyrotomin was synthesized using solid‐phase peptide synthesis and the structure examined with two‐dimensional nuclear magnetic resonance (NMR) spectroscopy.Two‐dimensional correlation experiments (COSY and TOCSY) enabled the assignment of many of the resonances. Conventional NOESY experiments did not produce inter‐residue information, however the alternative rotating frame NOE experiment (ROESY) resulted in intra‐residue αN, and sequential αN and NN NOES, permitting the sequence‐specific assignment of all resonances. The presence of few additional short‐range NOES and the absence of any long‐range NOES in the ROESY spectra indicated a lack of persistent secondary structure. The results from circular dichroism (CD) spectroscopy experiments were consistent with the NOE data, as addition of high concentrations of the denaturant urea produced no changes in the lophyrotomin CD spectrum. This conclusion was further supported by 13C spin‐lattice relaxation studies, which indicated that the peptide is a flexible molecule by examination of the α‐carbon chemical shifts, and by amide proton exchange rate measurements. Consequently it appears that if this peptide has to adopt a well defined structure to exert its biological activity it must do so on interaction with other molecules, such as a receptor.
Human parathyroid hormone: efficient synthesis in Escherichia coli using a synthetic gene, purification and characterization
Authors: OSHIKA YURI , YAMADA TAKAO , NAKAGAWA SHIZUE , FUJISHIMA AKIRA , KAWASE MASAHIRO , ISHIBASHI YOSHIHIRO , FUKUDA TSUNEHIKO 
Published: August 2010

Human parathyroid hormone is a peptide hormone consisting of 84 amino acid residues. Production of small proteins by direct expression in Escherichia coli is often unsuccessful owing to susceptibility of the mRNA and/or the product to endogenous enzymes. In this study, direct expression of the hormone at an excellent level (over 100 mg/L) has been achieved by using a suitably designed synthetic gene under the control of the T7 promoter.The protein produced in bacteria was extracted and easily purified in a good yield of 27 mg/L. The purified product was physico‐chemically identified as intact human parathyroid hormone from the results of amino acid analysis, N‐terminal sequencing, and peptide mapping using fast atom bombardment mass spectrometry. In biological assays the purified product stimulated adenylate cyclase in vitro, promoted bone growth and increased the serum osteocalcin in rats to the same extent as the authentic hormone.
Echistatin: the refined structure of a disintegrin in solution by 1 H NMR and restrained molecular dynamics
Authors: ATKINSON R.A. , SAUDEK V. , PELTON J.T. 
Published: August 2010

The structure of the disintegrin echistatin has been determined by 1H NMR, distance geometry calculations and restrained molecular dynamics simulations. The structure has been refined from the preliminary distance geometry calculations with the inclusion of additional 1H NMR data and hydrogen bonds identified in early stages of the molecular dynamics calculations. The calculations reported here allow a distinction to be made between the two possible disulfide bridging patterns ‐ echistatin is crosslinked as follows: Cys2‐Cysll, Cys7‐Cys32, Cys8‐Cys37, Cys20‐Cys39. The final set of structures gives an average pairwise root mean square distance of 0.100 nm (calculated over the backbone atoms of residues Ser4‐Cys20 and Asp30‐Pro40).The core of echistatin is a well defined though irregular structure, composed of a series of non‐classical turns crosslinked by the disulfide bridges and stabilised by hydrogen bonds. The RGD sequence is located in a protruding loop whose stem is formed by two rigid, hydrogen‐bonded strands (Thr18‐Cys20, Asp30‐Cys32). The RGD sequence is connected to this structure by short, flexible segments. High (but not unlimited) mobility is probably necessary for fast recognition and fitting to the integrin receptors. Sequence variability among the disintegrins is found in the segments flanking the RGD sequence, suggesting that these may be important in conferring specificity for the receptors.
Structure and solubility of interleukin‐2 in sodium dodecyl sulfate
Authors: ARAKAWA TSUTOMU , PHILO JOHN , KENNEY WILLIAM C. 
Published: August 2010

The solubility of an interleukin‐2 (C125A) in an aqueous sodium dodecyl sulfate (SDS) solution was examined as a function of SDS concentration. A stock interleukin‐2 solution at 1.1 or 0.31 mg/mL was mixed with one‐tenth volume of a stock SDS solution at various concentrations. At intermediate SDS concentrations, the interleukin‐2 showed nearly complete precipitation, while lower or higher SDS concentrations resulted in an increase in protein solubility. Circular dichroic analysis indicated that the protein remaining in the supernatant at low or high SDS concentrations has an altered conformation.Sedimentation velocity analysis of interleukin‐2 in 0.1%/SDS showed that about half the protein was monomeric, with the remainder as large aggregates with a broad size distribution from 20 to 100 S (Mr≊ 105‐107). In contrast, interleukin‐2 in 0.01% SDS has a much smaller distribution of aggregates, sedimenting at ca. 2–10 S.
Synthesis, crystal structure and conformation in solution of four stereoisomeric cyclo‐lanthionine derivatives
Authors: ÖSAPAY GEORGE , ZHU QIN , SHAO HUI , CHADHA RAJ K. , GOODMAN MURRAY 
Published: August 2010

The synthesis of the four stereoisomeric cyclo‐lanthionine derivatives: Cbz‐[RS]‐AlaL.‐[R S]‐AlaL‐OMe‐S
image

(where AlaL, denotes one end of the lanthionine unit) was carried out on a Kaiser‐oxime resin starting from orthogonally protected lanthionine units. The peptide ring was prepared in 79–85%, yield via amide bond formation by utilizing the method of peptide cyclization on an oxime resin (PCOR). The crystal and molecular structures of the protected cyclic dipeptides have been determined by X‐ray diffraction techniques. The two cyclic lanthionine derivatives with chiralities of [R.S] and [S.R] crystallized in the orthorhonibic space group P212121 and the [R.R]‐ and [S.S]‐cyclo‐lanthionine derivatives in the monoclinic space group C2. The structures were solved by direct methods and refined to an R factor of 0.0368–0.0573. The ring amide bonds in all four compounds are cis, while the urethane group is trans and extended. The NMR spectra of the four stereoisomers in DMSO‐d6 were used to determine their conformation in solution. The analysis of the NMR data with constrained distance geometry search showed the same conformational features in solution as in the crystalline state.
Variability analysis of the T‐cell receptors using three variability indexes
Authors: ALMAGRO JUAN C. , ZENTENO ROBERTO , VARGAS‐MADRAZO ENRIQUE , LARA‐OCHOA FRANCISCO 
Published: August 2010

In the absence of a three‐dimensional structure for TCR molecules, several attempts to identify their hyper‐variable regions by variability methods have been made; this subject is still troublesome. In this paper three different variability indexes were used: (i) the Kabat index, which is the classical measure of sequence variability, (ii)the modified Kabat index, successfully used in the β‐chain of T‐cell receptors and (iii) an information‐theoretical entropy concept, recently proposed as an improved measure of the variability. In order to identify the hypervariable regions in the TCR sequences, a Fourier filtering was applied on each variability profile.Results show that the three variability indexes have distinct resolutions for different levels of variability. Thus, the simultaneous use of these indexes compensates for the deficiency of any one of them in estimating variability. Applying the Fourier filtering, it is found that the hypervariable regions here identified, roughly coincide with the defined CDR‐2 and CDR‐3 in TCR by analogy with Ig. However, no hypervariable in the CDR‐1 of α‐ and β‐chains was found. The study on the influence of sample size in variability analysis, indicates that results are independent of the sample size. Considering current structural models of TCR‐peptide‐MHC interaction, one can suggest that the low‐variability characteristics of these regions is inherently related to the interaction with relatively conserved region on the α‐helices of MHC. © Munksgaard 1995.
The role of the C‐terminus of the insulin B‐chain in modulating structural and functional properties of the hormone
Authors: LEYER SIGMAR , GATTNER HANS‐GREGOR , LEITHÄUSER MARGOT , BRANDENBURG DIETRICH , WOLLMER AXEL , HÖCKER HARTWIG 
Published: August 2010

In memoriam Howard S. TagerWithin the scope of structure‐function studies on the proteohormone insulin, the role of the C‐terminal segment B26‐B30 for self‐association and receptor interaction was analyzed. Insulin derivatives with modifications in the region B26‐B30 were synthesized by trypsin‐catalyzed coupling reactions of des‐(B23‐B30)‐insulin with synthetic peptides. The peptides were obtained by Fmoc solid‐phase peptide synthesis. Insulins with multiple amino acid → glycine substitutions were examined to distinguish between the influence of the side chains and the influence of the main chain in positions B27‐B30 on the self‐association of the hormone. The analogues [GlyB27,B28,B29,B30]insulin and [GlyB27,B28,B30]insulin exhibit relative receptor affinities of 80% and self‐associate. The successive extension of [AlaB26]des‐(B27‐B30)‐insulin‐B26‐amide (relative receptor binding 273%) with amino xids corresponding to the native sequence B27‐B30 showed the influence of the length of the B‐chain on receptor affinity: the extension by B27‐threonine amide reduces receptor binding to 71%, all further prolongations have only small effects on the binding. The effect of the B28‐side chain on main‐chain conformation, self‐association and receptor binding was examined with [XB28]des‐(B29‐B30)‐insulin‐B28‐amides (X = Phe, Gly, D‐Pro). While the glycine and D‐proline analogues (relative binding 104 and 143%, respectively) retain the self‐association properties typical of insulin, [PheB28]des‐(B29‐B30)‐insulin‐B28‐amide (relative binding 50%) shows diminished self‐association. The backbone‐modified insulin derivative [SarB26]des‐(B27‐B30)‐insulin‐B26‐amide (sarcosine =N‐methylglycine) exhibits an unexpectedly high receptor affinity of 1100% which demonstrates that the B26‐amide hydrogen of the native hormone is not important for receptor binding. © Munksgaard 1995.
Amino‐acid sequence of bone Gla protein from the African clawed toad Xenopus laevis and the fish Sparus aurata1
Authors: CANCELA M. LEONOR , WILLIAMSON MATTHEW K. , PRICE PAUL A. 
Published: August 2010

As an initial step in the analysis of bone Gla protein (BGP; osteocalcin) function in lower vertebrates, we have developed a simple and rapid method for the isolation of BGP from bone and have applied this to the isolation of BGP from the African clawed toad Xenopus laevis and the fish Sparus aurutu. We have also determined the complete amino‐acid sequence of Sparus and Xenopus BGP, including the identification of the sites of γ‐carboxylation.Since the addition of Xenopus and Sparus BGP sequences significantly extends the range of species whose BGP structures are known, we have compared the 18 presently known BGP sequences. Twelve amino acids are invariant in these 18 RGP sequences and are therefore presumably critical to BGP conformation or function. Eight of these 12 invariant amino acids are also invariant in all presently known matrix Gla protein sequences (shark, mouse, rat, cow, human), an observation which strongly supports the evolutionary relationship between these two vitamin K‐dependent bone proteins and suggests that the proteins may adapt similar tertiary structures. © Munksgaard 1995.
Acid catalysis in the formation of dioxopiperazines from peptides containing tetrahydroisoquinoline‐3‐carboxylic acid at position 2
Authors: CAPASSO SANTE , SICA FILOMENA , MAZZARELLA LELIO , BALBONI GIANFRANCO , GUERRINI REMO , SALVADORI SEVERO 
Published: August 2010

The kinetics of the spontaneous formation of 2,5‐dioxopiperazines from peptides containing the Tic (1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid) residue in the 2‐position of the sequence has been studied in DMSO and water solution.The reaction is first order in Tic‐peptide and subject to general‐acid catalysis. Moreover, only the fraction of peptide having the amino terminal group in the deprotonated state reacts with appreciable rate. In pure organic solvent, and in aqueous solution with low buffer concentration, the degradation reaction of Tic‐peptides is very low; at 20°C for the peptide H‐Tyr‐Tic‐Phe‐Phe‐NH2, in DMSO and in neutral water in the absence of buffer, the half‐lives (t1/2) are 3 × 104 and 1.2 × 104 h, respectively. The addition of carboxylic acids or buffers to the reaction solutions markedly increases the reaction rate; in 0.01 M HAc in DMSO and in 0.1 M phosphate buffer in water, pH 7.1, t1/2 values for the tetrapeptide are 61 and 121 h, respectively. © Munksgaard 1995.
Coupling in the absence of tertiary amines. V Removal of the 2‐nitrobenzenesulfenyl (NPS) group with 1‐hydroxybenzotriazole in the presence of aniline or N‐methylaniline
Authors: BEDNAREK MARIA A. , BODANSZKY MIKLOS 
Published: August 2010

In a search for conditions of acidolytic removal of amine protecting groups leading to salts of the deblocked amine that can be acylated without addition of a tertiary amine, cleavage of the 2‐nitrobenzenesulfenyl (Nps) group with hydroxybenzotriazole (HOBt) in 2,2,2‐trifluoroethanol was attempted. The Nps group was smoothly removed, but the resulting salt of the amine component could not be acylated unless deprotonated with a tertiary base. A rationale is now proposed for this unsatisfactory outcome of the cleavage reaction and for the concomitant surprising reduction of HOBt to benzotriazole.Based on the proposed mechanism, a new approach was designed for the removal of the Nps group. It was cleaved with HOBt in the presence of weakly basic nucleophiles such as aniline, N‐methylaniline or 8‐aminoquinoline. The protecting group was transferred smoothly to the amino group of the nucleophilic acceptor leaving the deblocked amine component in the form of its HOBt salt. This was then readily acylated without addition of a tertiary amine. © Munksgaard 1995.
The role of oxidative stress in renovascular hypertension
Authors: Campos Ruy R , Oliveira‐Sales Elizabeth B , Nishi Érika E , Boim Mirian A , Dolnikoff Miriam S , Bergamaschi Cássia T 
Published: August 2010

Summary1. There is mounting evidence that increased oxidative stress and sympathetic nerve activity play important roles in renovascular hypertension. In the present review, we focus on the importance of oxidative stress in two distinct populations of neurons involved with cardiovascular regulation: those of the rostral ventrolateral medulla (RVLM) and those of the paraventricular nucleus of the hypothalamus (PVN) in the maintenance of sympathoexcitation and hypertension in two kidney–one clip (2K1C) hypertensive rats. Furthermore, the role of oxidative stress in the clipped kidney is also discussed.2. In the studies reviewed in this article, it was found that hypertension and renal sympathoexcitation in 2K1C rats were associated with an increase in Angiotensin II type one receptor (AT1) expression and in oxidative markers within the RVLM, PVN and in the clipped kidneys of 2K1C rats. Furthermore, acute or chronic anti‐oxidant treatment decreased blood pressure and sympathetic activity, and improved the baroreflex control of heart rate and renal sympathetic nerve activity in 2K1C rats. Tempol or vitamin C administration in the RVLM, PVN or systemically all reduced blood pressure and renal sympathetic activity. Cardiovascular improvement in response to chronic anti‐oxidant treatment was associated with a downregulation of AT1 receptors, as well as oxidative markers in the central nuclei and clipped kidney.3. The data discussed in the present review support the idea that an increase in oxidative stress within the RVLM, PVN and in the ischaemic kidney plays a major role in the maintenance of sympathoexcitation and hypertension in 2K1C rats.
Disruption of morphine‐conditioned place preference by a δ2‐opioid receptor antagonist: study of μ‐opioid and δ‐opioid receptor expression at the synapse
Authors: Billa Sophie K. , Xia Yan , Morón Jose A. 
Published: August 2010

AbstractThe addictive properties of morphine limit its clinical use. Learned associations that develop between the abused opiate and the environment in which it is consumed are engendered through Pavlovian conditioning processes. Disruption of the learned associations between the opiate and environmental cues may be a therapeutic approach to prevent morphine dependence. Although a role for the δ‐opioid receptor in the regulation of the rewarding properties of morphine has already been shown, in this study we further characterized the role of the δ‐opioid receptor in morphine‐induced conditioned responses by examining the effect of a selective δ2‐opioid receptor antagonist (naltriben), using a conditioned place preference paradigm in rats. Additionally, we used a subcellular fractionation technique to analyze the synaptic localization of μ‐opioid and δ‐opioid receptors in the hippocampus, in order to examine the molecular mechanisms that may underlie this morphine‐induced conditioned behavior. Our data show that the administration of 1 mg/kg naltriben (but not 0.1 mg/kg) prior to morphine was able to block morphine‐induced conditioned place preference. Interestingly, this naltriben‐induced disruption of morphine conditioned place preference was associated with a significant increase in the expression of the δ‐opioid receptor dimer at the postsynaptic density. In addition, we also observed that morphine conditioned place preference was associated with an increase in the expression of the μ‐opoid receptor in the total homogenate. Overall, these results suggest that modulation of the δ‐opioid receptor expression and its synaptic localization may constitute a viable therapeutic approach to disrupt morphine‐induced conditioned responses.
Effect of low‐dose cisapride on gastric emptying and QTc interval in preterm infants
Authors: Costalos C , Gounaris A , Varhalama E , Kokori F , Alexiou N , Katsarakis I 
Published: August 2010

The aim of the study was a prospective survey of the effects of low‐dose cisapride on gastric emptying and QTc interval in very low birthweight infants. Twenty low birthweight infants were studied: mean (SD) gestation 30.5 (2.2) wk; birthweight 1320 (150)g. Gastric emptying was assessed ultrasonically in 15 of these infants, in a randomized blind crossover study, following 24‐h low‐dose oral cisapride administration (0.1 mg/kg given 8 hourly), or placebo. The QTc interval was also determined in all 20 infants following a 7‐d course of cisapride or placebo. Conclusions: Cisapride significantly shortened both gastric emptying time and QTc interval (p < 0.05) compared to placebo. All infants completed the study without any apparent adverse effects. In conclusion, low‐dose cisapride administration significantly improves gastric emptying without increasing the QTc interval.
Acute rheumatic fever associated with Henoch‐Schönlein purpura: report of three cases and review of the literature
Authors: Eisenstein EM , Navon‐Elkan P 
Published: August 2010

Aim: To describe a possible relationship between Henoch‐Schönlein purpura and rheumatic fever. Methods: Patients with features of both diseases were identified by reviewing the hospital records. Medline and reference lists from published articles were used to search for previous reports of the two conditions occurring simultaneously. Results: Three newly described cases, and three previous reports of Henoch‐Schönlein purpura associated with rheumatic carditis or chorea were identified. Conclusions: The coexistence of these two disorders in some patients supports the view that Group A streptococcus may have a pathogenic role in Henoch‐Schönlein purpura.
Bifurcation Buckling Versus Limit Load Instabilities of
Elastic-Plastic Tubes Under Bending and External Pressure
Authors: Ju G. T. , Kyriakides S. 
Published: August 2010

Abstract
Commonly used procedures for installing offshore pipelines can induce substantial bending to the line in the presence of external pressure. These combined loads can lead to catastrophic collapse of the structure. For typically used steels and higher diameter-to-thickness ratios (D/t), bending is limited by a bifurcation type of instability; for lower D/t values, the structures exhibit limit load types of instabilities. Similar distinctions can be made for bending in the presence of external pressure. Previous work (Corona and Kyriakides, 1988) addressed primarily the limit load types of instabilities. In this paper, this analysis is extended to include bifurcation instabilities. The predictions from the two types of analyses are critically compared to experimental results and recommendations about the regime of applicability of each are made.