bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of the multiple antigenic peptides (MAP) strategy to the production of prophormone convertases antibodies: Synthesis, characterization and use of 8‐branched immunogenic peptides
Authors: Basak Ajoy , Boudreault Alain , Chen Andrew , Chrétien Michel , Seidah Nabil G. , Lazure Claude 
Published: May 2005

AbstractAntiserum against an N‐terminal sequence of murine prohormone convertase‐1 (mPC1) incorporating the sequence immediatley following the junction between the putative pro‐region and the active enzyme was obtained. This was accomplished using the multiple antigenic peptide (MAP) approach whereupon an 8‐branched polylysine core to which are grafted multiple copies of a 16 amino acid peptide representing the N‐terminal sequence of mPC1 (positions 84–99) was synthesized by solid‐phase Fmoc chemistry. The ensuing peptide was purified and fully characterized by RP‐HPLC, 1H‐NMR, amino acid composition, peptide sequencing and ion‐spray mass spectrometry. The immunological properties of the resulting antibodies in detecting recombinant PC1 in both crude and purified preparations were compared with antibodies raised against a similar N‐terminal segment of PC1 but using the conventioanl method of peptide–carrier protein conjugation and also developed against a C‐terminal fusion protein of PC1. Our data indicate that the MAP antibody was as efficient as both the amino and carboxy‐terminal antibodies in qualitative as well as quantitative analysis of PC1 encoded protein by radioimmunoassay. Following an identical approach, antibodies against other prohormone convertases like furin, PC5/6 and PACE4 were also developed and subsequently applied to a number of biochemical and immunological studies. In each case, the ease of preparation and high immunogenicity of the MAP approach were confirmed and reside in the simplicity and rapidity with which a potent and useful antiserum is obtained.
Inversion of 310‐helix screw sense in a (D‐αMe)Leu homotetrapeptide induced by a guest D‐(αMe)val residue
Authors: Formaggio Fernando , Crisma Marco , Toniolo Claudio , Benedetti Ettore , Di Blasio Benedetto , Saviano Michele , Galdiero Stefania , Kamphuis John , Santini Antonello 
Published: May 2005

AbstractThe terminally blocked tetrapeptide pBrBz‐[D‐(αMe)Leu]2‐D‐(αMe)Val‐D‐(αMe)Leu‐OtBu is folded in the crystal state in a left‐handed 310‐helical structure stabilized by two consecutive 1 ← 4 CO ⃛HN intramolecular H‐bonds, as determined by X‐ray diffraction analysis. A CD study strongly supports the view that this conformation is also that largely prevailing in MeOH solution. A comparison with the published conformation of pBrBz‐[D‐(αMe)Leu]4‐OtBu indicates that incorporation of a single internal β‐branched (αMe)Val guest residue into the host homo‐tetrapeptide from the γ‐branched (αMe)Leu residue is responsible for a dramatic structural perturbation, i.e. an inversion of the 310 screw sense from right to left‐handed.
Inclusion volume solid‐phase synthesis
Authors: Eichler Jutta , Houghten Richard A. , Lebl Michal 
Published: May 2005

AbstractSolid‐phase synthesis of peptides was carried out using only the volume of the solvent included in the swollen solid‐phase resin beads [inclusion volume synthesis]. This approach enables (i) the use of higher concentrations of activated amino acids, resulting in increased coupling rates, (ii) drastically decreased consumption of solvents, and (iii) the construction of multiple peptide synthesizers having virtually no reaction vessels.
Crystal Structure and Molecular Conformation of the Cyclic Hexapeptide cyclo‐(Gly‐Aib‐Gly)2
Authors: Escudero Encarnacion , Vidal Xavier , Solans Xavier , Peggion Evaristo , Subirana Juan Antonio 
Published: May 2005

AbstractWe have synthesized and crystallized the cyclic peptide (Gly‐Aib‐Gly) 2. Its structure has been determined by conventional X‐ray diffracti on methods. In the crystal it adopts a conformation with one β‐turn (type I) and its mirror image at the other side of the ring. All conformation al angles are similar to those reported for these amino acid residues. In particular the Aib residue has a conformation intermediate between α‐ and 310‐helical conformations. The ring is an adequate model for the β‐turn conformation. A molecule of formic acid is found in the crystal which shows a very short hydrogen bond with one of the glycine carbonyl groups.
The Solution Structure of the Immunodominant and Cell Receptor Binding Regions of Foot‐and‐mouth Disease Virus Serotype A, Variant A
Authors: Pegna M. , Molinari H. , Zetta L. , Gibbons W. A. , Brown F. , Rowlands D. , Siligardi G. , Mascagni P. 
Published: May 2005

AbstractThe solution structure of a 20 amino acid long peptide corresponding to the region 141–160 of the envelope protein Vp1 from foot‐and‐mouth disease virus (FMDV) serotype A, variant A, has been determined by a combination of NMR experiments and computer calculations. The peptide contains both the immunodominant epitope as well as the sequence (RGD) used by the virus to bind the cell receptor in the initial stages of infection. These two sites have been shown to partially overlap.One hundred and thirty‐five NMR distance constraints were used to obtain a set of 11 structures by distance geometry, minimization and molecular dynamics simulations. These structures were divided into two homogeneous families based upon backbone superimposition. The first and most populated family was characterized by a backbone RMS of 1.5±0.4 Å, the second by a backbone RMS of 0.8±0.2 Å. The two families had similar structural features and differed mainly in the backbone angles of G149. In the larger of the two families these angles favoured the formation of a loop comprising residues 147 to 152 and stabilized by a H‐bond between the NH of D147 and the CO of A152. In the second family, where this bond was absent, the peptide adopted in this region the shape of an irregular helix. The C‐terminal half of the peptide (152–159) was similar in both families and largely helical. Similar structural features were also found within the VRGDS sequence (144–148) which was assigned to a β‐turn type IV. The features of the two families of structures were found to be different from those of the recently published X‐ray structure of the antigenic loop of a chemically modified form of FMDV. Proposals accounting for these differences are provided which take into account the dual activity of the 141–160 sequence (i.e. antibody binding and cell invasion through receptor binding).
The Solution Conformational Features of Two Highly Homologous Antigenic Peptides of Foot‐and‐mouth Disease Virus Serotype A, Variants A and USA, Correlate with their Serological Properties
Authors: Pegna M. , Molinari H. , Zetta L. , Melacini G. , Gibbons W. A. , Brown F. , Rowlands D. , Chan E. , Mascagni P. 
Published: May 2005

AbstractThe solution structure of a peptide corresponding to the VP1 region 141–160 of foot‐and‐mouth disease virus (FMDV) serotype A variant USA has been studied by NMR and computer calculations and compared with the results from a study on a highly homologous peptide deriving from serotype A, variant A. The two peptides differ in their serological behaviour and contain the immunodominant epitope of the virus which partly overlaps with its receptor binding region. Distance constraints, derived both from 2D and 3D homonuclear NMR and 2D‐heteronuclear NMR experiments, were combined with DG calculations to yield 50 structures. After refinement through EM and restrained molecular dynamics simulations the selected structures shared several general features. In particular the 151–158 region was a helix in all cases while a large loop similar to that found in peptide A but comprising less residues and stabilized by an H‐bond between the side chains of D147 and S150 was found in the majority of structures. A further loop, common to all structures, was identified around the RGD sequence (145–147). This was different from that found in the corresponding region of peptide A as were the conformations of the individual residues within the RGDX sequence.The different structural features shown by the two peptides were rationalized in terms of the S148 (peptide A) to F148 (peptide USA) mutation. The second mutation, that at position 153 (L in A, P in USA) did not appear to affect the structure of the peptide significantly although the different dimensions of the loop in the central region and the type of H‐bond stabilizing it could be potentially ascribed to this second mutation.All criteria used pointed to different structural features for the two peptides consistent with their serological behaviour.
Synthesis of a New Template with a Built‐in Adjuvant and Its Use in Constructing Peptide Vaccine Candidates Through Polyoxime Chemistry
Authors: Zeng Weiguang , Jackson David C. , Rose Keith 
Published: May 2005

AbstractSynthetic lipopeptides are showing promise as vaccine candidates, but until now it has been very difficult to prepare them in homogeneous form. We describe the synthesis and characterization of a new water‐soluble, four‐branched template with a built‐in lipophilic adjuvant (Pam3Cys). Through the use of oxime chemistry, we attached four copies of an unprotected influenza virus peptide and characterized the product (13kDa) by reversed‐phase HPLC and electrospray ionization mass spectrometry. Several other such constructions were made using the new template and different peptides. We seem to have a general method for making synthetic lipopeptides in homogeneous form.
Effects of End Group and Aggregation on Helix Conformation: Crystal Structure of Ac‐(Aib‐Val‐Ala‐Leu)2‐Aib‐ OMe
Authors: Karle I. L. , Flippen‐Anderson J. L. , Uma K. , Balaram P. 
Published: May 2005

AbstractThe role of end groups in determining stereochemistry and packing in hydrophobic helical peptides has been investigated using an α‐aminosobutyric acid (Aib) containing model nonapeptide sequence. In contrast to the Boc‐analogue, Ac‐(Aib‐Val‐Ala‐Leu)2‐Aib‐OMe crystallizes with two independent molecules in a triclinic cell. The cell parameters are: space group P1, a=10.100(2)Å, b=15.194(4) Å, c=19.948(5) Å, α=63.12(2)°, β=88.03(2)°, γ=88.61(2)°, Z=2, R=7.96% for 5140 data where |Fo|>3σ(F). The two independent molecules alternate in infinite columns formed by head‐to‐tail hydrogen bonding. The helices in the two independent molecules are quite similar to each other but one molecule is rotated ≈︁123° about its helix axis with respect to the other. All the helical columns pack parallel to each other in the crystal. Replacement of the bulky Boc group does not lead to any major changes in conformation. Packing characteristics are also similar to those observed for similar helical peptides.
A Combinatorial Peptide Library Around Variation of the Human Immunode ficiency Virus (HIV‐1) V3 Domain Leads to Distinct T Helper Cell Responses
Authors: Estaquier Jérôme , Boutillon Christophe , Georges Bertrand , Ameisen Jean Claude , Tartar André , Auriault Claude 
Published: May 2005

AbstractThe hypervariable domain of the HIV gp120, the V3 loop domain, represents a target for neutralizing antibodies and for HIV vaccine strategies. In this study, we have investigated in murine species the potential cross‐reactivity of immune responses elicited by immunization either with individual V3 peptides, derived from distinct HIV sequences (BRU, RF, SF2, MN and ELI sequences), or with a V3 combinatorial peptide library.We observed that individual V3 peptides are immunogenic but elicit a specific B‐ and T‐cell immune response that is mainly restricted to the sequence of the immunizing peptide. In particular, T‐cell responses that depend on T‐cell receptor recognition of peptides bound to the molecules encoded by the major histocompatibility complex were significantly influenced by small differences in the peptide amino acid sequence. The combinatorial V3 peptide library, previously described as B‐ and T‐cell immunogens, induced a more broadly reactive immune response, specially when T‐cell cytokine secretion was used as a readout for restimulation of T‐cells with individual V3 peptides.These data suggest that amino acid variations in the sequence of an antigenic peptide could lead to the induction of different transducing signals in the primed T‐cell population and to the activation of T‐cells with distinct cytokine secretion properties. These observations may have implications in the understanding of antigenic variability and in the design of vaccine strategies.
The Importance of the Peptide Bond at Position 2 in HCO‐Met‐Leu‐Phe‐OMe Analogues as shown by Studies on Human Neutrophils
Authors: Cavicchioni Giorgio , Breveglieri Angela , Boggian Marisa , Vertuani Gianni , Reali Eva , Spisani Susanna 
Published: May 2005

AbstractThe formylpeptides formyl‐methionyl‐Nmethylleucyl‐ phenylaline methyl ester [for‐Met‐(NMe)Leu‐Phe‐OMe] 1, formyl‐methionyl‐2‐aminotetralin‐2‐carboxyl‐phenylalanine methyl ester [for‐Met Act‐Phe‐OMe] 2, formyl‐methionyl‐1,2,3,4‐terahydroisoquinoline‐3‐carboxl‐ phenylalanine methyl ester [for‐Met‐Tic‐Phe‐OMe] 3 and formyl‐ methionyl‐2‐aminoxy‐4‐methylvaleryl‐phenylalanine methyl ester [for‐Met‐OLeu‐Phe‐OMe] 4 were synthesized in order to investigate the role of the amide bond at position 2 on biological activities on human neutrophils. Only analogue 2, which keeps the NH group at position 2, was found to retain activity though sterically encumbered.
δ‐Selective Opioid Peptides Containing a Single Aromatic Residue in the Message Domain: An NMR Conformational Analysis
Authors: Crescenzi Orlando , Amodeo Pietro , Cavicchioni Giorgio , Guerrini Remo , Picone Delia , Salvadori Severo , Tancredi Teodorico , Temussi Piero A. 
Published: May 2005

AbstractThe sequence of deltorphin I, a δ‐selective opioid agonist, has been systematically modified by inserting conformationally constrained Cα,α disubstituted apolar residues in the third position. As expected, substitution of Phe with Ac6c, Ac5c and Ac3c yields analogues with decreasing but sizeable affinity. Surprisingly, substitution with Aib yields an analogue with almost the same binding affinity of the parent compound but with a greatly increased selectivity. This is the first case of a potent and very selective opioid peptide containing a single aromatic residue in the message domain, that is, only Tyr1. Here we report a detailed conformational analysis of [Aib3]deltorphin I and [Ac6c3]deltorphin I in DMSO at room temperature and in a DMSO/water cryomixture at low temperature, based on NMR spectroscopy and energy calculations. The peptides are highly structured in both solvents, as indicated by the exceptional finding of a nearly zero temperature coefficient of Val5 NH resonance. NMR data cannot be explained on the basis of a single structure but it was possible to interpret all NMR data on the basis of a few structural families. The conformational averaging was analysed by means of an original computer program that yields qualitative and quantitative composition of the mixture. Comparison of the preferred solution conformations with two rigid δ‐selective agonists shows that the shapes of [Aib3]deltorphin I and [Ac6c3]deltorphin I are consistent with those of rigid agonists and that the message domain of opioid peptides can be defined only in conformational terms.
Solid‐phase Synthesis and Cellular Localization of a C‐ and/or N‐terminal Labelled Peptide
Authors: Vidal P. , Chaloin L. , Méry J. , Lamb N. , Lautredou N. , Bennes R. , Heitz F. 
Published: May 2005

AbstractWe report the solid‐phase synthesis by the Fmoc strategy of a peptide containing a cysteamide group at its C‐terminus. This peptide was subject to further modifications including the linkage of fluorophores, namely lucifer yellow and coumarin respectively, at the C‐ and/or N‐terminals. After incubation with living cultured cells these two probes were localized and it is concluded that the post‐synthesis modifications can strongly modify the localization of the peptide.
Structural Polymorphism of Gramicidin A Channels: Ion Conductivity and Spectral Studies
Authors: Sychev Sergei V. , Sukhanov Stanislav V. , Barsukov Leonid I. , Ivanov Vadim T. 
Published: May 2005

AbstractThe relation between the various spatial structures of the gramicidin A channels and their ionic conductance has been studied. For this aim, various conformations of the peptide were pre‐formed in liposomal bilayer and after subsequent fusion of liposomes with planar lipid bilayer the measured channel conductance was correlated with gramicidin structures established in liposomes. To form the single‐stranded π6.3π 6.3 helix the peptide and lipid were co‐dissolved in TFE prior to liposome preparation. THF and other solvents were used to form parallel (↑ ↑ π π) and antiparallel (↑ ↓ π π) double helices. Conformation of gramicidin in liposomes made by various phosphatidylcholines was monitored by CD spectroscopy, and computer analysis of the spectra obtained was performed. After fusion of gramicidin containing liposomes with planar bilayer membranes from asolectin, the histograms of single‐channel conductance were obtained. The histograms had one or three distinct peaks depending on the liposome preparation. Assignment of the structure of the channel to conductance levels was made by correlation of CD data with conductance histograms. The channel‐forming analogue, des(Trp‐Leu)2‐gramicidin A, has been studied by the same protocol. The channel conductances of gramicidin A and the shortened analogue increase in the following order: ↑ ↓ π π 2 ↑ ↑ π π < π 6.3π6.3. Single‐channels formed by double helices have higher dispersity of conductance than the π6.3π6.3 helical channel. Lifetimes of the double helical and the π6.3π6.3 helical channels are very close to each other. The data obtained were compared with theoretically predicted properties of double helices [1].
The Structures of the Frenatin Peptides from the Skin Secretion of the Giant Tree Frog Litoria Infrafrenata
Authors: Raftery M. J. , Waugh R. J. , Bowie J. H. , Wallace J. C. , Tyler M. J. 
Published: May 2005

AbstractThe granular dorsal glands of the giant tree frog Litoria infrafrenata contain five peptides including caerulein (a known neuropeptide), and four new peptides named frenatins 1 (MH+ = 1140 Da), 2 (1423), 3 (2180) and 4 (2493). The amino acid sequences of the frenatins are detailed: their structures do not correspond to those of peptides isolated from other amphibians or animals. Frenatin 3, Gly‐Leu‐Met‐Ser‐Val‐Leu‐Gly‐His‐Ala‐Val‐Gly‐Asn‐Val‐Leu‐Gly‐ Gly‐Leu‐Phe‐Lys‐Pro‐Lys‐Ser‐(OH), has wide spectrum antimicrobial properties.
Synthesis of Fragments of the Peptide Component of Pseudobactin
Authors: Okonya John F. , Kolasa Teodozyj , Miller Marvin J. 
Published: May 2005

AbstractPseudobactin is a structurally complex and physiologically important siderophore (microbial iron chelator) from Pseudomonas putida‐ fluorescens. Various fragments of the unusual peptide component of pseudobactin listed below were prepared by solution‐phase peptide synthesis.L‐Lys· D‐threo‐β‐OH Asp· L‐Ala· D‐allo‐Thr· L‐AlaL‐Lys· D‐threo‐βOH Asp· L‐Ala· D‐allo‐ThrD‐threo‐β‐OH Asp· L‐Ala· D‐ allo‐Thr· L‐Ala· D‐N‐OH‐cycloOrnD‐threo‐β‐OH‐Asp· L‐Ala· D‐allo‐Thr· L‐AlaL‐Ala· D‐allo‐Thr· L‐ Ala· D‐N‐OH‐cycloOrnA class of related peptides named pseudomycins have shown promising antifungal activity. To examine if these peptide fragments above would elicit similar activity, the fragments were tested and found to have no antifungal activity in limited bioassays.
Conformational Analysis of Neuropeptide Y Segments by CD, NMR Spectroscopy and Restrained Molecular Dynamics
Authors: Gurrath Marion , Bisello Alessandro , Bottazzo Katia , Chung Chun‐Wa , Mammi Stefano , Peggion Evaristo 
Published: May 2005

AbstractNeuropeptide Y (NPY), a peptide amide comprising 36 residue has been shown to act as a potent vasoconstrictor. In order to shed light on the structural requirements for the biological activities with respect to the different prerequisites for affinity to the NPY receptor subtypes Y1 and Y2, in the present study the syntheses and conformational analyses of two C‐terminal segments, NPY(18–36) and NPY(13–36), are described.The results obtained by CD measurements, two‐dimensional NMR spectros copy and a conformational refinement of the NMR‐derived structure by molecular mechanics simulations support the findings of previously published structure –activity relationship studies for biologically active and selective compounds. In particular, the α‐helical conformation as well as an appropriate exposure of the side chains of the critical C‐terminal dipeptide within NPY(18–36) are in agreement with the prerequisites proposed for Y2 receptor binding of that segment.
Hydrophobic Effects on Antibacterial and Channel‐forming Properties of Cecropin A–Melittin Hybrids
Authors: Juvvadi Padmaja , Vunnam Satyanarayana , Merrifield Elizabeth L. , Boman Hans G. , Merrifield R. B. 
Published: May 2005

AbstractThe design of cecropin–melittin hybrid analogues is of interest due to the similarities in the structure of the antimicrobial peptides cecropin and melittin but differences in their lytic properties. We suspected that a hydrophobic residue in position 2 of milittin (Ile8 in the hybrid) plays an important role in the activity of the 15‐residue hybrid, KWKLFKKIGAVLKVL‐NH2, [CA(1–7)M(2–9)NH2] and have now examined its role in the analogue toward five test bacteria. Deletion of Ile8 reduced activity, and it was not restored by lengthening to 15 residues by addition of another threonine at the C‐terminus. Replacement of Ile8 by a hydrophobic leucine maintained good activity and Ala8 was equally active for four organisms, although less active against Staphylococcus aureus. Replacement by the hydrophilic Ser8 strongly reduced potency against all five organisms. Deletion of Leu15 decreased activity, but addition of Thr16 maintained good activity. The presence of hydrophobic residues appears to have a significant effect on the process of antibacterial activity. These peptide analogues showed voltage‐dependent conductance changes and are capable of forming ion‐pores in planar lipid bilayers. The antibacterial action of the peptides is thought to be first an ionic interaction with the anionic phosphate groups of the membrane followed by interaction with the hydrocarbon core of the membrane and subsequent reorientation into amphipathic α‐helical peptides that form pores (ion‐channels), which span the membrane. The analogue also showed an increase in α‐helicity with an increase in hexafluoro 2‐propanol concentration.