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1. |
Soluble neutral metallopeptidases: physiological regulators of peptide action |
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Journal of Peptide Science,
Volume 6,
Issue 6,
2000,
Page 251-263
Corie N. Shrimpton,
A. Ian Smith,
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摘要:
AbstractClassically, the pre‐ and post‐secretory processing of peptide signals appears to be mediated primarily by subtilisin‐like peptidases in secretory vesicles and/or membrane‐associated neutral endopeptidases in the extracellular environment. This article presents both biochemical and physiological evidence to support a role for soluble neutral metallopeptidases in the mediation of cell‐to‐cell communication by the selective generation and termination of peptide signals. These soluble peptidases have been implicated in the normal and disease‐state processing of peptides involved in neurological, endocrine and cardiovascular functions. In this context, specific inhibitors of these enzymes could selectively modulate peptide levels and thus have considerable therapeutic potential. The aim of this review is to discuss the design and development of specific inhibitors of soluble neutral metallopeptidases that have been instrumental in identifying the roles of these enzymes. It will also review the evidence and present a case for the involvement of soluble neutral metallopeptidases in the regulation of peptide signalling in both central nervous system (CNS) and peripheral tissues. Copyright © 2000 European Peptide Society and John W
ISSN:1075-2617
DOI:10.1002/1099-1387(200006)6:6<251::AID-PSC266>3.0.CO;2-O
出版商:John Wiley&Sons, Ltd.
年代:2000
数据来源: WILEY
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2. |
The deprotection of Lys(Mtt) revisited |
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Journal of Peptide Science,
Volume 6,
Issue 6,
2000,
Page 264-270
Line Bourel,
Olivier Carion,
Hélène Gras‐Masse,
Oleg Melnyk,
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摘要:
AbstractThe selective deprotection of Lys(Mtt)‐containing peptidyl resins was successfully monitored by RP‐HPLC using very short linear gradients. RP‐HPLC analyses of the acidic filtrates also revealed the partial cleavage of the Trt groups and of the peptide–resin bond. The absorbance of the Mtt carbocation at 470 nm is only twice that of the Trt cation. Thus, the UV monitoring at 470 nm seems to be inappropriate, especially at the end of the deprotection, when the Mtt and the Trt levels are comparable. Copyright © 2000 European Peptide Society and John Wiley&S
ISSN:1075-2617
DOI:10.1002/1099-1387(200006)6:6<264::AID-PSC248>3.0.CO;2-A
出版商:John Wiley&Sons, Ltd.
年代:2000
数据来源: WILEY
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3. |
Required structure of cationic peptide for oligonucleotide‐binding and ‐delivering into cells |
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Journal of Peptide Science,
Volume 6,
Issue 6,
2000,
Page 271-279
Takuro Niidome,
Masato Wakamatsu,
Akihiro Wada,
Toshiya Hirayama,
Haruhiko Aoyagi,
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摘要:
AbstractImprovement of the methods for oligonucleotide delivery into cells is necessary for the development of antisense therapy. In the present work, a new strategy for oligonucleotide delivery into cells was tested using cationic peptides as a vector. At first, to understand what structure of the peptide is required for binding with an oligonucleotide, several kinds of α‐helical and non‐α‐helical peptides containing cationic amino acids were employed. As a result, the amphiphilic α‐helix peptides were best for binding with the oligonucleotide, and the long chain length and large hydrophobic region in the amphiphilic structure of the peptide were necessary for the binding and forming of aggregates with the oligonucleotide. In the case of non‐α‐helical peptides, no significant binding ability was observed even if their chain lengths and number of cationic amino acid residues were equal to those of the α‐helical peptides. The remarkable ability of oligonucleotide delivery into COS‐7 cells was observed in the α‐helical peptides with a long chain length and large hydrophobic region in the amphiphilic structure, but was not observed in the non‐α‐helical peptides. It is considered that such α‐helical peptides could form optimum aggregates with the ODN for uptake into cells. Based on these results, the α‐helical peptide with a long chain length and large hydrophobic region is applicable as a vector for the delivery of oligonucleotides into cells. Copyright © 2000 European Pepti
ISSN:1075-2617
DOI:10.1002/1099-1387(200006)6:6<271::AID-PSC249>3.0.CO;2-F
出版商:John Wiley&Sons, Ltd.
年代:2000
数据来源: WILEY
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4. |
Optically active aromatic amino acids. Part VI. Synthesis and properties of [Leu5]‐enkephalin analogues containingO‐methyl‐L‐tyrosine1with ring substitution at position 3′ |
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Journal of Peptide Science,
Volume 6,
Issue 6,
2000,
Page 280-289
Zdzisław S. Arnold,
Peter W. Schiller,
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摘要:
AbstractTwelve new [Tyr(Me)1, Leu5]‐enkephalin analogues with substituents at position 3′ of the Tyr ring have been synthesized using traditional solution methods. The substituents were CO2H, CONH2, CO2Me, (E)′‐CHNOH, (E)‐CHNOMe and CH2OH. The analogues wereC‐terminated with methyl esters, amides or as free acids. In thein vitrobiological assays a remarkable agonist activity to the opiate receptor μ in guinea pig ileum (GPI) relative to Leu‐ENK was shown by the following: Leu‐ENK, 100; [Tyr(Me)(3′‐CO2Me)1, Leu‐OMe5]‐ENK (I), 8.1; [Tyr(Me)(3′‐(E)‐CHNOH)1, Leu‐OMe5]‐ENK (VI), 26.2; [Tyr(Me)(3′‐(E)‐CHNOH)1, Leu‐OH5]‐ENK (VII), 2.9; [Tyr(Me)(3′‐(E)‐CHNOH)1, Leu‐NH2 5]‐ENK (VIII), 4.7; and [Tyr(Me)(3′‐CH2OH)1, Leu‐OMe5]‐ENK (X), 5.6. The agonist effect was naltrexone‐ or naloxone‐reversible. The masking of the hydroxyl group in (E)‐hydroxyiminomethyl group of analogue (VI) byO‐methylation has totally abolished its GPI agonist activity. It seems that the (E)‐CHNOH group shows affinity and plays an analogous role to the phenol group Tyr1in leucine–enkephalin and in the tyramine group of the opiate alkaloids. The analogues: [Tyr(Me)(3′‐CO2Me)1, Leu‐OMe5]‐ENK (I), [Tyr(Me)(3′‐CO2H)1, Leu‐OMe5]‐ENK (II), [Tyr(Me)(3′‐CO2Me)1, Leu‐NH25]‐ENK (III), [Tyr(Me)(3′‐CO2H)1, Leu‐NH25]‐ENK (IV), [Tyr(Me)(3′‐CONH2)1, Leu‐NH25]‐ENK (V), [Tyr(Me)(3′‐(E)‐CHNOH)1, Leu‐OMe5]‐ENK (VI), [Tyr(Me)(3′‐(E)‐CHNOH)1, Leu‐OH5]‐ENK (VII), [Tyr(Me)(3′‐(E)‐CHNOH)1, Leu‐NH25]‐ENK (VIII), [Tyr(Me)(3′‐(E)‐CHNOMe)1, Leu‐OMe5]‐ENK (IX), [Tyr(Me)(3′‐CH2OH)1, Leu‐OMe5]‐ENK (X), [Tyr(Me)(3′‐CH2OH)1, Leu‐OH5]‐ENK (XI) and [Tyr(Me)(3′‐CH2OH)1, Leu‐NH25]‐ENK (XII) under testing had no significant agonist activity to the enkephalinergic receptor in mouse vas deferens (MVD). All methyl esters of synthesized analogues of [Leu5]‐ENK showed higher activity to μ receptors tha
ISSN:1075-2617
DOI:10.1002/1099-1387(200006)6:6<280::AID-PSC252>3.0.CO;2-0
出版商:John Wiley&Sons, Ltd.
年代:2000
数据来源: WILEY
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5. |
Carbopeptides: chemoselective ligation of peptide aldehydes to an aminooxy‐functionalizedD‐galactose template |
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Journal of Peptide Science,
Volume 6,
Issue 6,
2000,
Page 290-299
Jesper Brask,
Knud J. Jensen,
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摘要:
AbstractMultifunctional, topological template molecules such as linear and cyclic peptides have been used for the attachment of peptide strands to form novel protein models of, for example, 4‐α‐helix bundles. The concept of carbohydrates as templates forde novodesign of potential protein models has been previously described and these novel chimeric compounds were termedcarbopeptides. Here, a second generation strategy in which carbopeptides are synthesized by chemoselective ligation of a peptide aldehyde to an aminooxy‐functionalized α‐D‐galactopyranoside is described. This template was prepared by per‐O‐acylation of methyl α‐D‐galactopyranoside withN,N‐Boc2‐aminooxyacetic acid to form a tetra‐functionalized template, followed by treatment with TFA‐CH2Cl2to release the aminooxy functionality. The peptide aldehydes Fmoc‐Ser‐Gly‐Gly‐H and H‐Ala‐Leu‐Ala‐Lys‐Leu‐Gly‐Gly‐H were synthesized by a BAL strategy. Four identical copies of peptide aldehyde were smoothly attached to the template by chemoselective ligation to form a 2.1 and a 2.9 kDa carbopeptide, respectively. Copyright © 2
ISSN:1075-2617
DOI:10.1002/1099-1387(200006)6:6<290::AID-PSC257>3.0.CO;2-L
出版商:John Wiley&Sons, Ltd.
年代:2000
数据来源: WILEY
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