bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic analogues of bradykinin
Authors: CHIPENS G.I. , MUTULIS F.K. , MYSHLYAKOVA N.V. , MISINA I.P. , VITOLINA R.O. , KLUSHA V.J. , KATAYEV B.S. 
Published: August 2010

A study of the biological activity of six bradykinin and kallidin cycloanalogues has revealed that all of them exhibit prolonged hypotensive activity except the inactive cyclo‐(ω‐aminododecanoyl‐ω‐aminododecanoyl‐bradykinin) (CADADB) when assayed in anaesthetized rats in vivo. The threshold dose of cyclo‐bradykinin (CB) in these experiments was found to be 250 μg/kg of body weight. A single dose (500 μg/kg) of this cyclopeptide produces a decrease in the arterial pressure of rats up to 40 mm Hg for more than 2 h. The hypotensive action of other cyclopeptides under the same conditions is characterized by the following values: cyclo‐[∍‐(L‐Lys1, Gly6)‐bradykinin] (CLGB), α‐L‐Arg‐cyclo‐[∍‐(L‐Lys1, Gly6)‐bradykinin] (ACLGB) and cyclo‐∍‐kallidin (CK) – 5 μg/kg, 50 μg/kg, 40 mm Hg, over 2 h; cyclo‐(ω‐aminododecanoyl‐bradykinin) (CADB) – 50 μg/kg, 250 μg/kg, 40 mm Hg, 35 min. Some cyclopeptides appeared to possess myotropic activity in vitro on isolated rat uterus preparations: CB (α = 0.52, pD2 = 7.86), CK (α = 1.0, pD2 = 7.56), CADB (α = 0.81, pD2 = 6.41). CLGB, ACLGB and CADADB failed to show myotropic activity. In contrast to CLGB and CADB, CK was hypotensive in dogs. CB acts as a weak antagonist of bradykinin (pA2 = 5.09 ± 0.06) on rat uterus in vitro.It is believed that the hypotensive action within this series of compounds is primarily determined by the cycle size, whilst their myotropic activity is due to the presence of a “common” fragment Arg‐Pro‐Pro.CD spectra of the bradykinin cycloanalogues were obtained in aqueous solution. On CLGB and CK spectra effects of CaCl2, solvent and pH changes were also examined. The CD spectra of the analogues resemble the spectrum of bradykinin, indicating a certain similarity of secondary structures of these compounds.
Synthesis and biological activity of carboxyl terminally extended dermorphins
Authors: MARASTONI MAURO , SALVADORI SEVERO , BALBONI GIANFRANCO , MARZOLA GIULIANO , DEGLIUBERTI ETTORE CIRO , TOMATIS ROBERTO 
Published: August 2010

Dermorphinoyl(DMR)‐glycine, DMR‐sarcosine and DMR‐glycyl‐arginine have been prepared in order to examine the effect of C‐terminal extension of dermorphin (H‐Tyr‐D‐Ala‐Phe‐Gly‐Tyr‐Pro‐Ser‐NH2) on opioid activity.On GPI preparation the addition of Gly, Sar, or Gly‐Arg to the carboxyl terminus of dermorphinoic acid was detrimental to μ activity: dermorphinoyl‐derivatives, in fact, retain only 5–20% of dermorphin potency.Following intracerebroventricular administration (tail‐flick test), whereas the analgesic activities of compounds showed the trend dermorphin >DMR‐Sar> DMR‐Gly‐Arg>DMR‐Gly>morphine, the nonapeptide displayed highest activity after subcutaneous injection in mice: DMR‐Gly‐Arg was 2.5 and 10 times more potent than dermorphin and morphine, respectively.
Complete primary structure of statherin, a potent inhibitor of calcium phosphate precipitation, from the saliva of the monkey, Macaca arctoides
Authors: SCHLESINGER DAVID H. , HAY DONALD I. , LEVINE MICHAEL J. 
Published: August 2010

Human saliva, which is supersaturated with respect to basic calcium phosphate salts, is stabilized primarily by the presence of two classes of phosphoproteins, statherin and the acidic proline‐rich proteins (PRP). These molecules act by inhibiting both primary (spontaneous) precipitation of calcium phosphates in saliva and secondary (surface induced) precipitation of these salts onto dental enamel. The complete amino‐acid sequences of several human PRP and the N‐terminal sequence of PRP from saliva of M. arctoides have been determined. Similarly, the complete sequence of statherin from human and M. fascicularis saliva is known. We now report the complete structure of statherin from the saliva of the stump‐tailed monkey, M. arctoides. The structure was determined by gas‐phase sequencing of intact statherin, elucidating positions 1‐26, and sequencing an unpurified mixture of tryptic peptides which elucidated the remaining positions through the C‐terminus (residue 42) of the molecule. This latter degradation produced an eight amino‐acid overlap with that of intact statherin and was confirmed by C‐terminal analysis and amino‐acid composition of native statherin. The complete amino‐acid sequence of M. arctoides statherin is:NH2‐Asp‐PSer‐PSer‐Glu‐Glu5‐Lys‐Phe‐Leu‐Arg‐Arg10‐Leu‐Arg‐Arg‐Phe‐Asp15‐Glu‐Gly‐Arg‐Tyr‐Gly20‐Pro‐Tyr‐Gln‐Pro‐Phe25‐Val‐Pro‐Pro‐Pro29Leu30‐Tyr‐Pro‐Gln‐Pro‐Tyr35‐Gln‐Pro‐Tyr‐Gln‐Pro40 ‐Gln‐Tyr‐COOHThis sequence differs from human statherin at positions 11, 12, 15, 16, 18, 25‐27, 38‐40 and from M. fascicularis statherin at positions 26 and 28.
Systematic study of substance P analogs
Authors: WANG JIAN‐XIN , BRAY ANDREW M. , DIPASQUALE ANGELA J. , MAEJI N. JOE , GEYSEN H. MARIO 
Published: August 2010

The multipin peptide synthesis technique, a method for simultaneous multiple peptide synthesis, was developed for large‐scale screening of oligopeptides [Geysenet al.(1984)Proc. Natl. Acad. Sci. USA, 81, 3998‐40021. A modification of the technique allows the peptides assembled on polyethylene pins to be cleaved in their native amide form and reconstituted into physiologically compatible solutions. In this study, the suitability of these peptides for quantitative receptor binding assay was evaluated.Substance P and 18 analogs, including a set ofN‐terminal truncated substance P and a set of naturally occurring substance P analogs, were synthesized by the multipin methods. An average yield of 20 ± 3 nmol of peptide per pin was obtained. The purity of the peptides was estimated to be ca. 90%. The binding activities of these peptides were determined in a competition assay against125I‐BHSP binding to a rat brain synaptosome preparation. The rank order of the affinities of these peptides depicted a typical pharmacological profile of central NK1 receptor. The IC50values obtained were also in good agreement with data reported by other groups using similar experimental conditions, except that bulk synthesized peptides were used. This study demonstrates that the peptides synthesized with the multipin technique are suitable for quantitative receptor studies, particularly for a high‐volume screening of bioactive peptides.
The pseudo‐βI‐turn
Authors: KESSLER H. , MATTER H. , GEMMECKER G. , DIEHL H.‐J. , ISERNIA C. , MRONGA S. 
Published: August 2010

Synthesis and conformational analysis of three cyclic hexapeptides cyclo(‐Gly1‐Pro2‐Phe3‐Val4‐Xra5‐Phe6), Xaa= Phe (I), D‐Phe (II) and D‐Pro (III), were carried out to examine the influence of proline on the formation of reverse turns and the dynamics of hydrophobic peptide regions. Assignment of all 1H and 13C resonances was achieved by homo‐ and heteronuclear 2D‐NMR techniques (TOCSY, ROESY, HMQC, HMQC‐TOCSY and HMBCS‐270). The conformational analysis is based on interproton distances derived from ROESY spectra and homo‐ and heteronuclear coupling constants (E.COSY, HETLOC and HMBCS‐270). For structural refinements restrained molecular dynamics (MD) simulations in vacuo and in DMSO were performed.Each peptide exhibits two conformations in DMSO solution due to cis‐trans isomerism about the Gly‐Pro peptide bond. Surprisingly the cis‐Gly‐Pro segment in the minor isomers is not involved in a βVI‐turn, but forms a turn structure with cis‐Gly‐Pro in the i and i+ 1 positions. Although no stabilizing hydrogen bond is found in this turn, the φ and ψ‐angles closely correspond to a βI‐turn [Pro2:φ(i+ 1) ‐60°, ψ(i+ 1) ‐30° Phe3: φ(i+ 2) ‐100°, ψ(i+ 2) ‐50°]. Hence we call this structural element a pseudo‐βI‐turn.As expected, in the dominating all‐trans isomers proline occupies the i+ 1 position of a standard βI‐turn. Therefore, cis‐trans isomerization of the Gly1‐Pro2 amide bond only induces a local conformational rearrangement, with minor structural changes in other parts of the molecule. However, the geometry of the other regions is affected by the chirality of the i+ 1 amino acid for both isomers (βI for Phe5, βII′ for D‐Phe5 or D‐Prp5).
Simultaneous multiple synthesis and selective conjugation of cyclized peptides derived from a surface loop of a meningococcal class 1 outer membrane protein
Authors: BRUGGHE HUMPHREY F. , TIMMERMANS HANS A.M , VAN UNEN LEONTINE MA , TEN HOVE G. JAN , VAN DE WERKEN GERRIT , POOLMAN JAN T. , HOOGERHOUT PETER 
Published: August 2010

Starting from the α‐(2,4‐diniethoxybcnzyl) ester of N‐(9‐fluorenylniethoxycarbonyl)aspartic acid [Fmoc‐Asp‐ODmb], side‐chain‐protected resin‐bound Fmoc‐peptides containing an Nc‐l‐(4,4‐dimethyl‐2,6‐dioxocyclohexylidenc)ethyl lysY1 [Lys(Dde)] residue were prepared. The C‐terminal dimethoxybenzyl esters of aspartic acid were removed with 1% trifluoroacetic acid and 10% anisole in dichloromethane, followed by Fmoc‐cleavage in the usual manner. The resin‐bound peptides were then cyclized using 1‐benzotriazolyloxy‐tris‐[N‐pyrrolidino]phosphonium hexafluorophosphate (PyBOP) in the presence of N‐methylmorpholine. The (dimethyldioxocyclohexylidene)ethyl groups of lysine were removed with 1% hydrazine hydrate in N,N‐dimethylacetarnide, and the liberated side‐chain amino functions were modified by reaction with pentafluorophenyl S‐acetylinercaptoacetate (SAMA‐OPfp). Finally, the peptides were side‐chain deprotected, with exception of the Lys(SAMA) residue. and cleaved from the solid support with trifluoroacetic acid/anisole/ water, 95/2.5/2.5. Cyclic peptides comprising 7–14 amino acid residues were obtained employing this procedure.As a model conjugation. cyclo[Thr‐Asn‐Asn‐Asn‐Leu‐Lys(SAMA)‐Thr‐Lys‐Asp] was coupled with bromoacetamide. The same peptide was also coupled with a bromoacetylpeptide to give a well defined peptide1 peptide conjugate. All peptides were conjugated to bromoacetylated tetanus toxoid for immunization purposes.
Solution conformational dynamics of the C‐terminal residues in endothelin‐1 and some analogues: a time‐resolved fluorescence study
Authors: COWLEY DAVID J. , PELTON JOHN T. 
Published: August 2010

The rotational relaxation times of the single tryptophan residues in endotherlin‐1, [Ala1,3,11,15]endothelin‐l, human pro‐endothelin‐1, the linear hexapeptide Ac‐His‐Leu‐Asp‐Ile‐Ile‐Trp which corresponds to the C‐terminal residues 16–21 in endothelin‐1, the cyclic pentapeptide BQ123, and several di‐ and tri‐peptides possessing C‐terminal tryptophan residues have been determined from time‐resolved fluorescence anisotropy decays obtained by phase/modulation techniques. Fluorescence lifetime distribution widths have also been examined as predictors of conformational heterogeneity/restriction.A significant contribution from a slow rotational component supports either the persistence, on the nanosecond timescale at least, of a non‐flexible α‐helical structure for the C‐terminal tail residues of endothelin‐1 in water as solvent, as seen in the X‐ray crystallographic structure, or the interaction of the C‐terminal tail residues 16–21 with the constrained disulfide‐bridged core residues 1–15. This slow rotational contribution is less evident in the linear, acyclic tetraalanine analogue but greatly increased in pro‐endothelin‐1.In BQ123 the fluorescence characteristics support the occurrence of a dominant rotameric form involving the indole sidechain of the d‐tryptophan residue (Cα‐Cβ torsion angle χ1of 60°, as previously determined by NMR).
Structure‐function relationships of des‐(B26‐B30)‐insulin
Authors: SPODEN MARTIN , GATTNER HANS‐GREGOR , ZAHN HELMUT , BRANDENBURG DIETRICH 
Published: August 2010

In order to study the role of the amino acid in position B25 and its environment in shortened insulins, a series of analogues was prepared with the following modifications; 1, Stepwise shortening of the B‐chain including replacements of TyrB26 and ThrB27 by glycine; 2, substitutions at the carboxamide nitrogen of des‐(B26‐B30)‐insulin‐B25‐amide by apolar, polar or charged residues of various chain lengths; 3, replacement of PheB25 by asparagine‐amide, phenylalaninol or a series of alkyl and aralkyl residues. Trypsin‐catalyzed semisyntheses were performed with Boc‐protected or unprotected des‐octapeptide‐(B23‐B30)‐insulin and synthetic peptides. Relative receptor binding and in vitro bioactivity of [AsnB25]‐des‐(B26‐B30)‐insuIin‐B25‐amide was 227 and 292% (on insulin), other activities ranged between 1 and ca. 200%.We make the following conclusions. An l‐amino acid is essential in position B25. The B25‐carbonyl and NH groups favour high binding and “superpotency”, but are not indispensible for receptor contacts. For high affinity receptor interaction, the planarity at the C2‐atom and the distance of B25‐side‐chain branching in position B25 are important, but an aromatic ring is not necessary.
Brain cathepsin B but not metalloendopeptidases degrade rAPP751 with production of amyloidogenic fragments
Authors: MARKS N. , BERG M.J. , SAPIRSTEIN V.S. , DURRIE R. , SWISTOK J. , MAKOFSKE R.C. , DANHO W. 
Published: August 2010

Lysosomal cathepsin B but not L degraded rAPP751 to yield C‐terminal 19–25 kDa fragments containingβA4, reinforcing the view that acidic proteases participate in endosonial‐lysosomal processing to yield amyloidogenic fragments in situ. This mechanism is consistent with fragmentation of endogenous APPs within clathrin‐coated vesicles (CVs) by vesicular hydrolases, with the appearance of C‐terminal amyloidogenic fragments following incubation at pH 6.5. A neutral endopeptidase resembling NEP 24.11 (PS‐NEP) purified from detergent extracts of human brain degraded rAPP751; however, breakdown was not blocked robustly by metal chelators or phosphoramidon, suggesting the presence of an alternative processing enzyme. Effects of other inhibitors showed that breakdonn was mediated b) serine‐protease‐like component(s). A phosphoramidon‐insensitive metalloendopeptidase (PI‐NEP) partially purified from rat brain P2 using detergents, and resembling NEP 24.15, showed no activity towards I‐rAPP751.Peptides containing putative β‐ or γ‐secretase sites were synthesized for purposes of examining their metabolism by the brain enzymes. Those containing β‐secretase sites were hydrolysed at one or more sites by the four enzymes, but only PI‐ and PS‐NEP acted at the Met‐Asp site of Ac‐VaI‐Lys‐Met‐Asp‐Ala‐Glu‐Phe‐Arg.NH2. In the case of substrates Containing the γ‐site, these two categories of enzymes were the only ones degrading N‐Ac‐Ilc‐Ala NH2. These data imply that the brain metalloendopeptidases, while inactive towards intact precursors, may be involved in turnover of intermediates containing β‐ or 7‐sites.
Influence of serine in positionion conformation and dynamics of reverse turns
Authors: MATTER H. , GEMMECKER G. , KESSLER H. 
Published: August 2010

NMR spectroscopy has been employed for the conformational analysis of the cyclic hexapeptide cycle(‐d‐Pro1‐Ala2‐Ser3(Bzl)‐Trp4‐Orn5(Z)‐Tyr6‐) with and without protecting groups on Ser3and Orn5. This peptide sequence was derived from the active loop sequence of the α‐amylase inhibitor Tendamistat (HOE 467). The aim was to investigate the role of serine in positioniof a standard β‐turn on the conformation and stabilization of this turn. Based on distance and torsion constraints from 2D NMR spectroscopic measurements in DMSO‐d6solution, structure refinement was accomplished by restrained molecular dynamics (MD) simulationsin vacuoand in DMSO.The analysis of both structures in solution reveals a considerable effect of the unprotected serine sidechain on the adjacent β‐turn conformation. While in the protected peptide with Ser3(Bzl) a βII‐turn is observed between Trp4and Orn5, the deprotected compound reveals a βI‐turn in this region. The βI‐turn is stabilized by a backbone‐sidechain hydrogen bond from Orn5NαH to Ser3Oγ. Comparisons with other NMR‐derived solution structures of cyclic model peptides and in some protein structures from literature reveal a general structural motif in the stabilization of βI‐turns by serine in theiposition through backbone‐sidechain interactions. © Munksgaard 1995.
Linear and cyclic synthetic peptides related to the main autophosphorylation site of the Src tyrosine kinases as substrates and inhibitors of Lyn †
Authors: RUZZA PAOLO , CALDERAN ANDREA , FILIPPI BRUNO , BIONDI BARBARA , DEANA ARIANNA DONELLA , CESARO LUCA , PINNA LORENZO A. , BORIN GIANFRANCO 
Published: August 2010

Tyrosine protein kinases (TPKs) of the src family contain two major phosphoacceptor sites which are homologous to the Tyr 416 and Tyr 527 of pp60c‐src. The former represents the main autophosphorylation sites of these enzymes, and its phosphorylation correlates with increased kinase activity.It has previously been demonstrated that the Src‐like tyrosine kinase expressed by the oncogene lyn displays a high affinity toward the heptapeptide H‐Glu‐Asp‐Asn‐Glu‐Tyr‐Thr‐Ala‐OH, which reproduces the main autophosphorylation site of the Src family enzymes [Donella‐Deana, A., Marin, O., Brunati, A.M. & Pinna, L.A. (1992) Eur. J. Biochem.204, 1159–1163].Our study was addressed to the synthesis of some derivatives of this sequence in order to obtain both peptide substrates suitable for the detection of the Src‐like tyrosine kinase activity and active site‐directed inhibitors specific for this class of enzymes. For this purpose we synthesized by classical solution methods the heptapeptide and its dimeric form. Moreover, in order to improve the proteolytic resistance of these peptides we also synthesized their cyclic derivatives and their N‐terminal acetylated and C‐terminal amidated analogs. The correlation between the different structural properties induced by the modifications of the native sequence and the propensity of the peptides to act as Lyn substrates was examined. The kinetic data obtained indicate that the extent of the peptide phosphorylation varies considerably depending on the flexibility and length of the analogs. While the cyclization and the C‐terminal amidation of the heptapeptide are detrimental for the Lyn activity, dimeric derivatives display very favourable kinetic constants. In particular the cyclic dimer is an especially suitable substrate for the tyrosine kinase and a powerful inhibitor of both the phosphorylation activity of Lyn and the enzyme autophosphorylation. © Munksgaard 1995.
Solid‐phase synthesis of H‐ and methylphosphonopeptides
Authors: HOFFMANN RALF , THOLEY ANDREAS , HOFFMAN THOMAS , KALBITZER HANS ROBERT 
Published: August 2010

We introduce solid‐phase syntheses of H‐ and methylphosphonopeptides, giving access for the first time to a new class of mimics for o‐phosphoamino acids. The model peptides H‐GlyGlyXaaAla‐OH (Xaa = Ser, Thr) were synthesized on a solid‐phase using Fmoc/tBu strategy and HBTU/HOBt activation by incorporation of hydroxyl‐protected serine and threonine. As selectively cleavable hydroxyl‐protecting groups we used triphenylmethyl and tert‐butyldimethylsilyl for both amino acids, as described in the literature. All peptides were phosphitilated with O,O‐di‐tert‐butyl‐N,N‐diethylphosphoramidite and yielded H‐phosphonopeptides after trifluoroacetic acid cleavage. Alternatively we phosphonylated the peptides with O‐tert‐butyl‐N,N‐diethyl‐P‐methylphosphonamidite, which was synthesized by a two‐step one‐pot procedure starting from commercially available chemicals. All H‐ and methylphosphonopeptides were obtained in high purities and yields, as shown by reversed‐phase high‐performance liquid chromatography and anion‐exchange chromatography.The phosphonopeptides were characterized by 1H and 31P NMR. We confirmed their molecular masses by electrospray mass spectrometry and analyzed their fragmentation schemes, which seemed to be characteristic for each class of analogues. The H‐phosphonopeptides lost phosphonic acid (H3PO3, 82 mass units) and the methylphosphonopeptides lost methylphosphonic acid (MeH2PO3, 96 mass units). Both H‐ and methylphosphonopeptides represent a new and simply accessible class of mimics for phosphopeptides. Compared with the corresponding phosphopeptides all phosphonopeptides were synthesized in higher yields and purities (>80%). © Munksgaard 1996.
Note on Water Drag on Sea Ice for Different Surface
Roughness
Authors: Myrhaug D. 
Published: August 2010

Abstract
The approach in Myrhaug [1], where a simple analytical theory describing the motion in a turbulent planetary boundary layer near a rough seabed was presented, is extended to smooth and transitional smooth-to-rough turbulent flow. An inverted boundary layer similar to that at the seabed is applicable under the sea ice. The water drag coefficient at the ice surface and the direction of the surface shear stress are presented for rough, smooth and transitional turbulent flows.
Model Tests on Multi-Tube Production Risers
Authors: Hartnup G. C. , Airey R. G. 
Published: August 2010

Abstract
Model tests carried out at 1/14.5 scale on two production risers in a towing tank are described. One of the risers considered is modeled on that used in the Buchan field, while the other has a compact low drag configuration of the same production capacity. The tensioning system was carefully modeled, and vessel surge motions were accurately represented in both regular and irregular waves. Current was represented by carriage motion. Some results are presented for bending moments and displacements for both models and comparisons are made with computer simulations to deduce appropriate values for hydrodynamic coefficients.
Low-Income Women with Abnormal Breast Findings: Results of a Randomized Trial to Increase Rates of Diagnostic Resolution
Authors: Bastani Roshan , Mojica Cynthia M. , Berman Barbara A. , Ganz Patricia A. 
Published: August 2010

Abstract
Background: Timely diagnostic resolution of abnormal breast findings represents a critical step in efforts to reduce breast cancer morbidity and mortality. Yet, follow-up rates among resource poor populations are not optimal. Efforts to mitigate this disparity are needed. We report results of a randomized trial assessing the effectiveness of a patient support and navigation intervention in increasing timely diagnostic resolution of abnormal breast findings among indigent women.
Methods: Women (n = 1,708) diagnosed with a breast abnormality at two public hospitals were randomized to an intervention or control group. The intervention, delivered through telephone, involved one call from a professional health worker and multiple calls from a lay health worker. The outcome, timely diagnostic resolution, defined as receipt of a definitive diagnosis (malignant or benign) within 6 months of the index referral, was assessed through medical chart audit.
Results: Intent-to-treat analyses revealed no significant effect of the intervention on timely diagnostic resolution. Diagnostic resolution rates were 55% and 56%, respectively, in the intervention and control arms. The significant predictors were method of abnormality identification (odds ratio = 1.50) and location of first scheduled appointment (odds ratio = 0.62).
Conclusions: The intervention was not effective in creating change within the County health system. Achieving optimum diagnostic follow-up may require more intensive interventions than the one tested. In addition, system-level rather than patient-level interventions may hold more promise.
Impact: There are no randomized trials reported in the literature testing interventions to increase diagnostic follow-up of breast abnormalities. Future research might test patient and system-level interventions that can be sustained beyond the study period. Cancer Epidemiol Biomarkers Prev; 19(8); 1927–36. ©2010 AACR.