bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of novel basic head‐to‐side‐chain cyclic dynorphin A analogs: Strategies and side reactions
Authors: Vig Balvinder S. , Murray Thomas F. , Aldrich Jane V. 
Published: February 2004

AbstractNovel N‐terminus‐to‐side‐chain cyclic analogs of the opioid peptide dynorphin (Dyn) A–(1–11)NH2 were prepared that retain the basicity of the N‐terminal amine and restrict the backbone conformation around the important Tyr1 residue. Cyclic peptides were synthesized in which the N‐terminal amine and the Nε‐amine of a Lys at position 3 or 5 were attached to the α‐carbon and carbonyl of an acetyl group, respectively. Several synthetic strategies were explored with detailed analysis of the side reactions in order to obtain the desired cyclic peptides. One of the side reactions observed involved premature loss of the N‐terminal 9‐fluorenylmethoxycarbonyl (Fmoc) group during the neutralization step following deprotection of the Mtt (4‐methyltrityl) protecting group from the side chain of Lys. The successful strategy involved the synthesis of the linear peptide up through Gly2 and functionalization through the Nε‐amine of Lys. A linear N‐terminal alkylated analog was prepared by alkylation of the peptide on the resin with an equimolar amount of bromoacetamide, followed by treatment of the peptide with Fmoc–OSu prior to cleavage from the resin to facilitate separation by reversed phase high performance liquid chromatography of unreacted peptide from the desired alkylated product. The novel N‐terminal cyclic Dyn A analogs and the linear analog were evaluated for their opioid receptor affinities. These peptides exhibited large losses in affinity for opioid receptors; the low affinity of the linear N‐terminal alkylated peptide suggested that the α‐acetamide group on the N‐terminal amine resulted in unfavorable interactions with opioid receptors. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2003
Local sequence information in cellular retinoic acid‐binding protein I: Specific residue roles in β‐turns*
Authors: Rotondi Kenneth S. , Gierasch Lila M. 
Published: February 2004

AbstractWe have recently shown that two of the β‐turns (III and IV) in the ten‐stranded, β‐clam protein, cellular retinoic acid‐binding protein I (CRABP I), are favored in short peptide fragments, arguing that they are encoded by local interactions (K. S. Rotondi and L. M. Gierasch, Biochemistry, 2003, Vol. 42, pp. 7976–7985). In this paper we examine these turns in greater detail to dissect the specific local interactions responsible for their observed native conformational biases. Conformations of peptides corresponding to the turn III and IV fragments were examined under conditions designed to selectively disrupt stabilizing interactions, using pH variation, chaotrope addition, or mutagenesis to probe specific side‐chain influences. We find that steric constraints imposed by excluded volume effects between near neighbor residues (i,i+2), favorable polar (i,i+2) interactions, and steric permissiveness of glycines are the principal factors accounting for the observed native bias in these turns. Longer‐range stabilizing interactions across the β‐turns do not appear to play a significant role in turn stability in these short peptides, in contrast to their importance in hairpins. Additionally, our data add to a growing number of examples of the 3:5 type I turn with a β‐bulge as a class of turns with high propensity to form locally defined structure. Current work is directed at the interplay between the local sequence information in the turns and more long‐range influences in the mechanism of folding of this predominantly β‐sheet protein. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2003
Side‐chain anchoring strategy for solid‐phase synthesis of peptide acids with C‐terminal cysteine
Authors: Barany George , Han Yongxin , Hargittai Balazs , Liu Rong‐Qiang , Varkey Jaya T. 
Published: February 2004

AbstractMany naturally occurring peptide acids, e.g., somatostatins, conotoxins, and defensins, contain a cysteine residue at the C‐terminus. Furthermore, installation of C‐terminal cysteine onto epitopic peptide sequences as a preliminary to conjugating such structures to carrier proteins is a valuable tactic for antibody preparation. Anchoring of Nα‐Fmoc, S‐protected C‐terminal cysteine as an ester onto the support for solid‐phase peptide synthesis is known to sometimes occur in low yields, has attendant risks of racemization, and may also result in conversion to a C‐terminal 3‐(1‐piperidinyl)alanine residue as the peptide chain grows by Fmoc chemistry. These problems are documented for several current strategies, but can be circumvented by the title anchoring strategy, which features the following: (a) conversion of the eventual C‐terminal cysteine residue, with Fmoc for Nα‐amino protection and tert‐butyl for Cα‐carboxyl protection, to a corresponding S‐xanthenyl (2XAL4) preformed handle derivative; and (b) attachment of the resultant preformed handle to amino‐containing supports. This approach uses key intermediates that are similar to previously reported Fmoc–XAL handles, and builds on earlier experience with Xan and related protection for cysteine. Implementation of this strategy is documented here with syntheses of three small model peptides, as well as the tetradecapeptide somatostatin. Anchoring occurs without racemization, and the absence of 3‐(1‐piperidinyl)alanine formation is inferred by retention of chains on the support throughout the cycles of Fmoc chemistry. Fully deprotected peptides, including free sulfhydryl peptides, are released from the support in excellent yield by using cocktails containing a high concentration (i.e., 80–90%) of TFA plus appropriate thiols or silanes as scavengers. High‐yield release of partially protected peptides is achieved by treatment with cocktails containing a low concentration (i.e., 1–5%) of TFA. In peptides with two cysteine residues, the corresponding intramolecular disulfide‐bridged peptide is obtained by either (a) oxidation, in solution, of the dithiol product released by acid; (b) simultaneous acidolytic cleavage and disulfide formation, achieved by addition of the mild oxidant DMSO to the cleavage cocktail; or (c) concomitant cleavage/cooxidation (involving a downstream S‐Xan protected cysteine), using reagents such as iodine or thallium tris(trifluoroacetate) in acetic acid. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2003
New tools for the control of peptide conformation and supramolecular chemistry: Crown‐carrier, Cα‐methyl L‐DOPA amino acids
Authors: Formaggio Fernando , Oancea Simona , Peggion Cristina , Crisma Marco , Toniolo Claudio , Wright Karen , Wakselman Michel , Mazaleyrat Jean‐Paul 
Published: February 2004

AbstractThe preferred conformation of five, terminally protected, model peptide series to the hexamer level, based on three novel crowned, Cα‐methyl L‐DOPA amino acids combined with either L‐Ala/Aib or Gly/Aib, were assessed in structure supporting solvents using FT‐IR absorption, 1H NMR, and CD techniques. The FT‐IR absorption spectra strongly suggest that the contribution of the crowned Cα‐tetrasubstituted residue to intramolecular H‐bonding is equivalent to that of Aib and is much more significant than that of either L‐Ala or Gly. In addition, the 1H NMR titrations and the CD patterns resemble those typically exhibited by (right‐handed) 310‐helical structures. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2003
Polar residue tagging of transmembrane peptides
Authors: Melnyk Roman A. , Partridge Anthony W. , Yip Jeannie , Wu Yanqiu , Goto Natalie K. , Deber Charles M. 
Published: February 2004

AbstractStudies that focus on packing interactions between transmembrane (TM) helices in membrane proteins would greatly benefit from the ability to investigate their association and packing interactions in multi‐spanning TM domains. However, the production, purification, and characterization of such units have been impeded by their high intrinsic hydrophobicity. We describe the polar tagging approach to biophysical analysis of TM segment peptides, where incorporation of polar residues of suitable type and number at one or both peptide N‐ and C‐termini can serve to counterbalance the apolar nature of a native TM segment, and render it aqueous‐soluble. Using the native TM sequences of the human erythrocyte protein glycophorin A (GpA) and bacteriophage M13 major coat protein (MCP), properties of tags such as Lys, His, Asp, sarcosine, and Pro‐Gly are evaluated, and general procedures for tagging a given TM segment are presented. Gel‐shift assays on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) establish that various tagged GpA TM segments spontaneously insert into micellar membranes, and exhibit native TM dimeric states. Sedimentation equilibrium analytical centrifugation is used to confirm that Lys‐tagged GpA peptides retain the native dimer state. Two‐dimensional nuclear magnetic resonance (NMR) spectroscopy studies on Lys‐tagged TM MCP peptides selectively enriched with N‐15 illustrate the usefulness of this system for evaluating monomer–dimer equilibria in micelle environments. The overall results suggest that polar‐tagging of hydrophobic (TM) peptides approach constitutes a valuable tool for the study of protein–protein interactions in membranes. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2003
Solution structures of cyclic melanocortin agonists and antagonists by NMR
Authors: Ying Jinfa , Kövér Katalin E. , Gu Xuyuan , Han Guoxia , Trivedi Dev B. , Kavarana Malcolm J. , Hruby Victor J. 
Published: February 2004

AbstractThe melanocortin receptors are involved in many physiological functions, including pigmentation, sexual function, feeding behavior, and energy homeostasis, making them potential targets for drugs to treat obesity, sexual dysfunction, etc. Understanding the conformational basis of the receptor–ligand interactions is crucial to the design of potent and selective ligands for these receptors. The solution structures of the cyclic melanocortin agonists, partial agonist, and antagonists MTII, VJH085, SHU9119, MK5, and MK9 were determined by two‐dimensional nuclear magnetic resonance (2D NMR) spectroscopy at pH 4.5 and 25 °C in water (90% H2O/10% D2O). The overall backbone structures of these cyclic α‐melanocyte‐stimulating hormone (α‐MSH) analogues around the message sequence (His6‐D‐Phe7/D‐Nal(2′)7‐Arg8‐Trp9) were similar and reasonably well defined. β‐Turns spanning His6 and D‐Phe7/D‐Nal(2′)7 were identified in all analogues, and an amphiphilic molecular surface was obtained for the message sequence residues in most structures within the NMR ensembles. The β‐turn, which most closely resembles a type II β‐turn, leads to stacking between the aromatic rings of His6 and D‐Phe7 in MTII and VJH085. However, no aromatic stacking between His6 and D‐Nal(2′)7 was found in structures of the D‐Nal(2′)7‐containing analogues. The difference in the side‐chain dispositions of His6 and D‐Nal(2′)7 may be responsible for the reduced potency or antagonist activity of the D‐Nal(2′)7‐containing analogues. In addition, our results suggest that the side‐chain orientations may also modulate the receptor selectivity. The information found in this study will be useful for the further design of ligands for melanocortin receptors. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2003
Dendritic oligoguanidines as intracellular translocators
Authors: Chung Hyun‐Ho , Harms Guido , Min Seong Churl , Choi Byung Hyune , Min Changhee , Taulane Joseph P. , Goodman Murray 
Published: February 2004

AbstractA series of polyguanidylated dendritic structures that can be used as molecular translocators have been designed and synthesized based on nonpeptide units. The dendritic oligoguanidines conjugated with fluorescein or with a green fluorescent protein (GFP) mutant as cargos were isolated and characterized. Quantification and time‐course analyses of the cellular uptake of the conjugates using HeLa S3 and human cervical carcinoma cells reveal that the polyguanidylated dendrimers have comparable translocation efficiency to the Tat(49–57) peptide. Furthermore, the deconvolution microscopy image analysis shows that they are located inside the cells. These results clearly show that nonlinear, branched dendritic oligoguanidines are capable of translocation through the cell membrane. This work also demonstrates the potential of these nonpeptidic dendritic oligoguanidines as carriers for intracellular delivery of small molecule drugs, bioactive peptides, and proteins. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004
Targeting duplex DNA with DNA‐PNA chimeras? Physico‐chemical characterization of a triplex DNA‐PNA/DNA/DNA
Authors: Petraccone L. , Erra E. , Messere A. , Montesarchio D. , Piccialli G. , De Napoli L. , Barone G. , Giancola C. 
Published: February 2004

AbstractTargeting double‐stranded DNA with homopyrimidine PNAs results in strand displacement complexes PNA/DNA/PNA rather than PNA/DNA/DNA triplex structures. Not much is known about the binding properties of DNA‐PNA chimeras. A 16‐mer 5′‐DNA‐3′‐p‐(N)PNA(C) has been investigated for its ability to hybridize a complementary duplex DNA by DSC, CD, and molecular modeling studies. The obtained results showed the formation of a triplex structure having similar, if not slightly higher, stability compared to the same all‐DNA complex. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Structure‐based design of novel nonpeptide inhibitors of the Src SH2 domain: Phosphotyrosine mimetics exploiting multifunctional group replacement chemistry*
Authors: Sundaramoorthi Raji , Kawahata Noriyuki , Yang Michael G. , Shakespeare William C. , Metcalf Chester A. , Wang Yihan , Merry Taylor , Eyermann Charles J. , Bohacek Regine S. , Narula Surinder , Dalgarno David C. , Sawyer Tomi K. 
Published: February 2004

AbstractA series of novel nonpeptide inhibitors of the pp60c‐Src (Src) SH2 domain is described that exploit multifunctional group replacement of the phenylphosphate moiety of phosphotyrosine (pTyr). Relative to an x‐ray structure of citrate complexed to the pTyr binding site of the Src SH2 domain, these nonpeptide ligands illustrate the systematic replacement of the phosphate group by multiple nonhydrolyzable, mono‐ or dianionic functionalities. Specifically, several phenylalanine (Phe) analogs incorporating key 4′ and 3′ substituents were synthesized and incorporated into a bicyclic benzamide template previously reported (W. C. Shakespeare et al., Proceedings of the National Academy of Science USA , 2000, Vol. 97, pp. 9373–9378). These pTyr mimetics included 4′,3′‐diphosphono‐Phe (Dpp), 4′,3′‐dicarboxymethyloxy‐Phe (Dcp), and 4′‐phosphono‐3′‐carboxymethyloxy‐Phe (Cpp). Noteworthy were nonpeptide inhibitors 8–11 that were 5‐ to 10‐fold more potent than the cognate tetrapeptide ligand Ac–pTyr–Glu–Glu–Ile–NH2 in binding to the Src SH2 domain. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2003
Binding of isofraxidin to bovine serum albumin
Authors: Liu Jiaqin , Tian Jianniao , Hu Zhide , Chen Xingguo 
Published: February 2004

AbstractThe binding of isofraxidin to bovine serum albumin (BSA) was studied under physiological conditions with BSA concentration of 1.5×10−6 mol · L−1 and drug concentration in the range of 1.67×10−6 mol · L−1 to 2.0×10−5 mol · L−1. Fluorescence quenching spectra in combination with uv absorption spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and CD spectroscopy was used to determine the drug‐binding mode, binding constant, and the protein structure changes in the presence of isofraxidin in aqueous solution. The linearity of Scatchard plot indicates that isofraxidin binds to a single class of binding sites on BSA and the values given for the binding constants agree very closely with those obtained by the modified Stern‐Volmer equation. The thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS), were calculated to be −17.63 kJ · mol−1 and 51.38 J · mol−1 · K−1 according to the van't Hoff equation, which indicated that hydrophobic interaction played a main role in the binding of isofraxidin to BSA. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Micellar environments induce structuring of the N‐terminal tail of the prion protein
Authors: Renner Christian , Fiori Stella , Fiorino Ferdinando , Landgraf Dirk , Deluca Dominga , Mentler Matthias , Grantner Klaus , Parak Fritz G. , Kretzschmar Hans , Moroder Luis 
Published: February 2004

AbstractIn the physiological form, the prion protein is a glycoprotein tethered to the cell surface via a C‐terminal glycosylphosphatidylinositol anchor, consisting of a largely α‐helical globular C‐terminal domain and an unstructured N‐terminal portion. This unstructured part of the protein contains four successive octapeptide repeats, which were shown to bind up to four Cu2+ ions in a cooperative manner. To mimic the location of the protein on the cell membrane and to analyze possible structuring effects of the lipid/water interface, the conformational preferences of a single octapeptide repeat and its tetrameric form, as well of the fragment 92–113, proposed as an additional copper binding site, were comparatively analyzed in aqueous and dodecylphosphocholine micellar solution as a membrane mimetic. While for the downstream fragment 92–113 no conformational effects were detectable in the presence of DPC micelles by CD and NMR, both the single octapeptide repeat and, in an even more pronounced manner, its tetrameric form are restricted into well‐defined conformations. Because of the repetitive character of the rigid structural subdomain in the tetrarepeat molecule, the spatial arrangement of these identical motifs could not be resolved by NMR analysis. However, the polyvalent nature of the repetitive subunits leads to a remarkably enhanced interaction with the micelles, which is not detectably affected by copper complexation. These results strongly suggest interactions of the cellular form of PrP (PrPc) N‐terminal tail with the cell membrane surface at least in the octapeptide repeat region with preorganization of these sequence portions for copper complexation. There are sufficient experimental facts known that support a physiological role of copper complexation by the octapeptide repeat region of PrPc such as a copper‐buffering role of the PrPc protein on the extracellular surface. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Aerobic phosphorus release linked to acetate uptake in bio‐P sludge: Process modeling using oxygen uptake rate
Authors: Guisasola Albert , Pijuan Maite , Baeza Juan A. , Carrera Julián , Casas Carles , Lafuente Javier 
Published: February 2004

AbstractThe main processes involved in enhanced biological phosphorus removal (EBPR) under anaerobic and subsequently aerobic conditions are widely described in the literature. Polyphosphate accumulating organisms (PAO) are the organisms responsible for this process. However, the mechanisms of PAO are not fully established yet under conditions that differ from the classical anaerobic/aerobic conditions. In this work, we made a comparison between the behavior of PAO under classical EBPR conditions and its behavior when consuming substrate under only aerobic conditions. In addition, oxygen uptake rate (OUR) was measured in the set of experiments under aerobic conditions to improve the characterization of the process. A kinetic and stoichiometric model based on Activated Sludge Model No.2 (ASM2) and including glycogen economy (AnOx model), calibrated for classical anaerobic/aerobic conditions, was not able to describe the experimental data since it underestimated the acetate consumption, the PHB storage, and the OUR. Two different hypotheses for describing the experimental measurements were proposed and modeled. Both hypotheses considered that PAO, under aerobic conditions, uptake acetate coupled to PHB storage, glycogen degradation, and phosphorus release as in anaerobic conditions. Moreover, the first hypothesis (PAO‐hypothesis) considered that PAO were able to store acetate as PHB linked to oxygen consumption and the second one (OHO hypothesis) considered that this storage was due to ordinary heterotrophic organisms (OHO). Both hypotheses were evaluated by simulation extending the AnOx model with additional equations. The main differences observed were the predictions for PHB degradation during the famine phase and the OUR profile during both feast and famine phases. The OHO hypothesis described the experimental profiles more accurately than the PAO hypothesis. © 2004 Wiley Periodicals, Inc.
Mechanical properties of desiccated ragweed pollen grains determined by micromanipulation and theoretical modelling
Authors: Liu T. , Zhang Z. 
Published: February 2004

AbstractThe mechanical properties of desiccated ragweed pollen grains were determined using a micromanipulation technique and a theoretical model. Single pollen grains with a diameter of approximately 20 μm were compressed and held, compressed and released, and compressed to rupture at different speeds between two parallel surfaces. Simultaneously, the force being imposed on the pollen grains was measured. It has been found that the rupture force of pollen grains increased linearly with their displacement at rupture on average, but was independent of their diameter. The mean rupture force was 1.20 ± 0.03 mN, and mean deformation (the ratio between the displacement and diameter) at rupture was 22 ± 0.6%. Single pollen grains were modeled as a capsule with a core full of air and a non permeable wall. A constitutive equation based on Hookean law was used to determine the mechanical property parameters Eh (product of the Young's modulus and wall thickness), and the mean value of Eh of desiccated pollen gains was estimated to be 1653 ± 36 N/m © 2004 Wiley Periodicals, Inc.
Oxidative burst, jasmonic acid biosynthesis, and taxol production induced by low‐energy ultrasound in Taxus chinensis cell suspension cultures
Authors: Wu Jianyong , Ge Xiuchun 
Published: February 2004

AbstractThis work aims to detect the two signal events in the elicitation of plant defense responses and secondary metabolism in plant cell cultures by low‐energy ultrasound (US), transient production of reactive oxygen species (ROS) or the oxidative burst and jasmonic acid (JA) biosynthesis, and examine their influence on secondary metabolism. Experiments were carried out in Taxus chinensis cell suspension culture which produces the anticancer diterpenoid Taxol (paclitaxel). The culture was exposed to low‐frequency US for a short period of time (2 min). At sufficiently high US power levels the US exposure significantly enhanced the Taxol production and slightly depressed cell growth and viability. The US exposure induced transient production of O and H2O2 and an increase in the intracellular JA level as well as the activities of enzymes for JA synthesis, lipoxygenase (LOX), and allene oxide synthase (AOS). Inhibition of the ROS production by putative ROS scavengers or the JA accumulation by LOX inhibitors effectively suppressed the US‐stimulated Taxol production. Inhibition of the ROS production also suppressed the US‐induced JA accumulation. These results suggest that oxidative burst is an upstream event to JA accumulation, and both ROS from the oxidative burst and JA from the LOX pathway are key signal elements in the elicitation of Taxol production of T. chinensis cells by low‐energy US. © 2004 Wiley Periodicals, Inc.