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1. |
Sweet and bitter taste: Structure and conformations of two aspartame dipeptide analogues |
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Journal of Peptide Science,
Volume 1,
Issue 6,
1995,
Page 349-359
Ettore Benedetti,
Enrico Gavuzzo,
Antonello Santini,
Darin R. Kent,
Yun‐Fei Zhu,
Qin Zhu,
Christian Mahr,
Murray Goodman,
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摘要:
AbstractThe synthesis and X‐ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compoundsL‐aspartyl‐D‐α‐methylphenylalanine methyl ester [L‐Asp‐D‐(αMe)Phe‐OMe] andL‐aspartyl‐D‐alanyl‐2,2,5,5‐tetramethylcyclopentanyl ester [L‐Asp‐D‐Ala‐OTMCP] elicit bitter and sweet taste, respectively. The C‐terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side‐chain carboxylate and the amino groups formaing a zwitterionic ring with a conformation defined by ψ,χX1 = 157.7°, −61.5° forL‐Asp‐D‐Ala‐OTMCP and 151.0°, −68.8° forL‐Asp‐D‐(αMe)Phe‐OMe. In the second residue, a left‐handed helical conformations is observed for the (αMe)Phe residue ofL‐Asp‐D‐(αMe)Phe‐OMe with ϕ2= 49.0° and ψ2= 47.9°, while the Ala residue ofL‐Asp‐D‐Ala‐OTMCP adopts a semi‐exextended conformation characterized by dihedral angles ϕ2= 62.8° and ψ2= −139.9°. The solid‐state structure of the bitterL‐Asp‐D‐(αMe)Phe‐OMe is extended; while the crystal structure of the sweetL‐Asp‐D‐OTMCP roughly adopts the typical L‐shaped structure shown by other sweeteners. The data ofL‐Asp‐D‐(αMe)Phe‐OMe are compared with those of its diastereoisomerL‐Asp‐L‐(αMe)Phe‐OMe. Conformati
ISSN:1075-2617
DOI:10.1002/psc.310010602
出版商:John Wiley&Sons, Ltd.
年代:1995
数据来源: WILEY
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2. |
Metal ion binding affinities of gastrin and CCK in membrane mimetic environments |
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Journal of Peptide Science,
Volume 1,
Issue 6,
1995,
Page 360-370
Jürgen Lutz,
Elisabeth Weyher,
Luis Moroder,
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摘要:
AbstractThe fully active gastrin and CCK analogues [Nle15]‐gastrin‐ 17 and [Nle, Thr]‐CCK‐9 were analysed for their Ca2+and Tb3+affinities in various membrane mimetic conditions. In TFE both gastrin and CCK exhibited high affinities for calcium and terbium. At saturation level identical metal ion/peptide ratios were determined with Ca2+and Tb3+, i.e.R= 3 for gastrin andR= 1 for CCK, confirming the very similar coordination properties of the two metal ions. The conformational effects of both metal ions were found to be very similar with a disordering effect in the case of gastrin and a conformational transition to β‐turn type structure in the case of CCK. In order to mimic more properly physiological conditions, similar experiments were performed in the prsence of phospholipid bilayers. No interaction of the peptides with the bilayers was observed even in the presence of phospholipid bilayers. No interaction of the peptides with the bilayers was observed even in the presence of mmolar Ca2+concentrations. Induced lipid interaction via N‐terminal lipodervatization of gastrin and CCK allowed to translocate quantitatively the two hormones into phospholipid bilayers and to examine the effect of extravesicular Ca2+on the conformation of the peptide headgroups and on their display at the water/lipid interphase. The CCK moiety of the lipo‐CCK inserted into phospholipid bilayers interacts with the lipid phase and addition of Ca2+enhances the clustering of the peptide headgroups in a more β‐sheet type conformation. Conversely, insertion of lipo‐gastrin into the bilayers leads to full exposure of the gastrin headgroup to the bulk water in predominantly random coil structure. Again Ca2+provokes aggregation. As the lipo‐peptide/phospholipid system still represents only an artificial model, it remains hazardous to derive a biological relevance from these data. The significantly higher affinity of lanthanide ions than Ca2+for the peptides could well play a role in the inhibibitory activity of lanthanum on the signal transduction of the C
ISSN:1075-2617
DOI:10.1002/psc.310010603
出版商:John Wiley&Sons, Ltd.
年代:1995
数据来源: WILEY
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3. |
Use of a gel‐forming dipeptide derivative as a carrier for antigen presentation |
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Journal of Peptide Science,
Volume 1,
Issue 6,
1995,
Page 371-378
Rolands Vegners,
Irina Shestakova,
Ivars Kalvinsh,
Robert M. Ezzell,
Paul A. Janmey,
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摘要:
AbstractA dipeptide of the formula Fmoc‐Leu‐Asp and some other related dipeptides were synthesized in solution by standard methods. When such peptides are dissolved in water at concentrations below 1% at 100 °C and cooled below 60 °C they form turbid solutions and eventaully visocelastic gels at lower temperatures. Such gels are thermoreversible and can also be disrupted by mechanical agitation. At a concentration of 2 mg/ml the peptide Fmoc‐Leu‐Asp forms an aqueous gel at 60 °C with a shear modulus of 80 Pa measured at a frequency of 1 rad/s. Peptide solutions undergo an abrupt increase in light scattering between 1 and 1.5 mg/ml at both 23 and 60 °C. By analogy with previous observations of other systems, this increse appears to be due to the formation of filamentous micelles and the aggregation of filamaents into a three‐dimensional network. When low molecular weight adamantanamine derivatives, which are inherently non‐antigenci antiviral drugs, were incorporated into the Fmoc‐Leu‐Asp gel and injected into rabbits, high titre specific antibodies were efficiently produced without the need for additional adjuvant. Both the physical properties of the gel and its effect on the antigenicity of low molecular weight compounds suggest a number of pra
ISSN:1075-2617
DOI:10.1002/psc.310010604
出版商:John Wiley&Sons, Ltd.
年代:1995
数据来源: WILEY
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4. |
Synthesis and biological characterization of a series of analogues of ω‐conotoxin gvia |
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Journal of Peptide Science,
Volume 1,
Issue 6,
1995,
Page 379-384
James P. Flinn,
Roger Murphy,
Jaroslav H. Boubliek,
Michael J. Lew,
Christine E. Writh,
James A. Angus,
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摘要:
AbstractThe 27‐residue polypeptide ω‐conotoxin GVIA (ω‐CgTx), from the venom of the cone shellConus geographus, blocks N‐type neuronal calcium channels. It contains three disulphide bridges. We reporte here the synthesis and biological characterization of a seires of analogues in which one disulphide has been replaced by substitution of appropriate Cys residues with Ser, viz. [Ser1,16]‐ω‐CgTx, [Ser8,19]‐ω‐CgTx, [Ser15,26]‐ω‐CgTx, [Ser16]‐ω‐CgTx8‐27and [Ser15]‐ω‐CgTx1‐19. All syntheses were conducted manually using either Boc or Fmoc methodology. Deprotected peptides were oxidized to their bridged forms using either aerial oxidation or aqueous dimethyl sulphoxide. Peptides were purified using RP‐HPLC, and their purity and identity were checked by RP‐HPLC, capillary electrophoresis and mass spectrometry. Inhibition of neuronal N‐type calcium channels was assessed as the inhibition of the twitch responses of rat vas deferens stimualted with single electrical pulses at 20 second intervals. None of these analogues was biologically active, suggesting that the disulphides play an impor
ISSN:1075-2617
DOI:10.1002/psc.310010605
出版商:John Wiley&Sons, Ltd.
年代:1995
数据来源: WILEY
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5. |
Application of the multiple antigenic peptides (MAP) strategy to the production of prophormone convertases antibodies: Synthesis, characterization and use of 8‐branched immunogenic peptides |
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Journal of Peptide Science,
Volume 1,
Issue 6,
1995,
Page 385-395
Ajoy Basak,
Alain Boudreault,
Andrew Chen,
Michel Chrétien,
Nabil G. Seidah,
Claude Lazure,
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摘要:
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 u
ISSN:1075-2617
DOI:10.1002/psc.310010606
出版商:John Wiley&Sons, Ltd.
年代:1995
数据来源: WILEY
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6. |
Inversion of 310‐helix screw sense in a (D‐αMe)Leu homotetrapeptide induced by a guestD‐(αMe)val residue |
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Journal of Peptide Science,
Volume 1,
Issue 6,
1995,
Page 396-402
Fernando Formaggio,
Marco Crisma,
Claudio Toniolo,
Ettore Benedetti,
Benedetto Di Blasio,
Michele Saviano,
Stefania Galdiero,
John Kamphuis,
Antonello Santini,
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摘要:
AbstractThe terminally blocked tetrapeptidepBrBz‐[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 CO ⃛HN 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 ofpBrBz‐[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 inversio
ISSN:1075-2617
DOI:10.1002/psc.310010607
出版商:John Wiley&Sons, Ltd.
年代:1995
数据来源: WILEY
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7. |
Masthead |
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Journal of Peptide Science,
Volume 1,
Issue 6,
1995,
Page -
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ISSN:1075-2617
DOI:10.1002/psc.310010601
出版商:John Wiley&Sons, Ltd.
年代:1995
数据来源: WILEY
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