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1. |
Amyloid β‐peptide interactions with neuronal and glial cell plasma membrane: binding sites and implications for Alzheimer's disease |
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Journal of Peptide Science,
Volume 10,
Issue 5,
2004,
Page 229-248
Yann Verdier,
Márta Zarándi,
Botond Penke,
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摘要:
AbstractThe extracellular accumulation of amyloid‐beta (Aβ) in neuritic plaques is one of the characteristic hallmarks of Alzheimer's disease (AD), a progressive dementing neurodegenerative disorder of the elderly. By virtue of its structure, Aβ is able to bind to a variety of biomolecules, including lipids, proteins and proteoglycans. The binding of the various forms of Aβ (soluble or fibrillar) to plasma membranes has been studied with regard to the direct toxicity of Aβ to neurons, and the activation of a local inflammation phase involving microglia.The binding of Aβ to membrane lipids facilitates Aβ fibrillation, which in turn disturbs the structure and function of the membranes, such as membrane fluidity or the formation of ion channels.A subset of membrane proteins binds Aβ. The serpin‐enzyme complex receptor (SEC‐R) and the insulin receptor can bind the monomeric form of Aβ. The α7nicotinic acetylcholine receptor (α7nAChR), integrins, RAGE (receptor for advanced glycosylation end‐products) and FPRL1 (formyl peptide receptor‐like 1) are able to bind the monomeric and fibrillar forms of Aβ. In addition, APP (amyloid precursor protein), the NMDA‐R (N‐methyl‐D‐aspartate receptor), the P75 neurotrophin receptor (P75NTR), the CLAC‐P/collagen type XXV (collagen‐like Alzheimer amyloid plaque component precursor/collagen XXV), the scavenger receptors A, BI (SR‐A, SR‐BI) and CD36, a complex involving CD36, α6β1–integrin and CD47 have been reported to bind the fibrillar form of Aβ.Heparan sulfate proteoglycans have also been described as cell‐surface binding sites for Aβ. The various effects of Aβ binding to these membrane molecules are discussed. Copyright © 2004 Eur
ISSN:1075-2617
DOI:10.1002/psc.573
出版商:John Wiley&Sons, Ltd.
年代:2004
数据来源: WILEY
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2. |
Cosolvent‐assisted oxidative folding of a bicyclic α‐conotoxin ImI |
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Journal of Peptide Science,
Volume 10,
Issue 5,
2004,
Page 249-256
Jacob S. Nielsen,
Pawel Buczek,
Grzegorz Bulaj,
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摘要:
Abstractα‐Conotoxin ImI is a 12‐amino acid peptide, found in the venom of the marine snailConus imperialis. This conotoxin is a selective antagonist of α7 nicotinic acetylcholine receptors. To produce biologically active α‐ImI, disulfide bonds must be formed between Cys2–Cys8 and Cys3–Cys12. Oxidative folding of bicyclic conotoxins, such as α‐ImI, has been traditionally achieved using two‐step oxidation protocols with orthogonal protection on two native pairs of cysteines. In this work, two alternative oxidation protocols were explored: (1) the recently described one‐pot oxidation of t‐butyl/4‐methylbenzyl protected Cys pairs and (2) direct oxidative folding. In contrast to the first method, the latter one resulted in high yields of correctly folded α‐ImI. The addition of organic cosolvents, such as methanol, ethanol or isopropanol into the folding mixture significantly increased the accumulation of the native peptide. This effect was also observed for another conotoxin, α‐PnIA. It is suggested that cosolvent‐assisted direct oxidation might be of general use for other bicyclic α‐conotoxins, but efficiency should be assessed on a case‐by‐case basis. Copyright © 2003 European P
ISSN:1075-2617
DOI:10.1002/psc.531
出版商:John Wiley&Sons, Ltd.
年代:2004
数据来源: WILEY
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3. |
Synthetic human insulin 4 does not activate the G‐protein‐coupled receptors LGR7 or LGR8 |
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Journal of Peptide Science,
Volume 10,
Issue 5,
2004,
Page 257-264
Feng Lin,
Laszlo Otvos,
Jin Kumagai,
Geoffrey W. Tregear,
Ross A. D. Bathgate,
John D. Wade,
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摘要:
AbstractIn contrast to the cellular receptors for insulin and insulin‐like growth factors that are known to be protein tyrosine kinases, those of both insulin 3 and relaxin have recently been identified as being members of the leucine‐rich repeat‐containing G‐protein coupled receptor (LGR) family, LGR8 and LGR7, respectively. This has prompted an examination into the possibility that they might also be specific for another member of the insulin superfamily, namely, insulin 4. Towards this aim, a two‐chain peptide corresponding to the predicted primary structure of insulin 4 was prepared by solid phase synthesis. As conventional aeration and combination of the two S‐reduced chains in solution at high pH failed to produce target product, selectively S‐protected A‐ and B‐chains were prepared followed by stepwise, individual formation of each of the three disulfides, one intramolecular within the A‐chain and two intermolecular. Chemical characterization confirmed the purity and identity of the synthetic insulin 4 analogue. However, secondary structural analysis indicated that the peptide was devoid of tertiary conformation suggesting that the native peptide may well be either significantly longer in length or is similar to insulin‐like growth factor I or II in that it is a single chain product. Screening of the synthetic analogue for activation of transfected cells bearing LGR7, and LGR7 splice variant or LGR8 failed to identify a specific interaction. Thus, thein vivostructural identity of insulin 4 and its receptor (if any) as well as its potential function remains unknown. Copyright © 2003 European Peptide Society an
ISSN:1075-2617
DOI:10.1002/psc.521
出版商:John Wiley&Sons, Ltd.
年代:2004
数据来源: WILEY
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4. |
Synthesis and characterization of a sulfated and a non‐sulfated cyclic CCK8 analogue functionalized with a chelating group for metal labelling |
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Journal of Peptide Science,
Volume 10,
Issue 5,
2004,
Page 265-273
Stefania De Luca,
Giancarlo Morelli,
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摘要:
AbstractTwo cyclic peptides, cyclo29, 34[Dpr29, Lys34(DTPA‐Glu)]‐CCK8 (1) and cyclo29, 34[Tyr27(SO3H), Dpr29, Lys34(DTPA‐Glu)]‐CCK8 (2), bearing the chelating moiety DTPA‐Glu covalently bound to the Lys side chain have been synthesized by solid‐phase methodology. The presence in compound2of many acidic functions characteristic of the chelating agent increases the lability of the sulfate group on the Tyr side chain. This finding suggests that prolonged acid treatments should be avoided during the preparation of such peptides. Sulfation of cyclo29, 34[Dpr29, Lys34(DTPA‐Glu)]‐CCK8 was performed using a pyridine–SO3complex as reagent. This reaction has been found to be the most suitable synthetic strategy for obtaining compound2in good yield. Cyclo29, 34[Tyr27(SO3H), Dpr29, Lys34(DTPA‐Glu)]‐CCK8 is a new promising CCK8 analogue, able to coordinate radioactive isotopes of metal ions such as111In(III), and to bind, in a selective way, the CCKA‐R receptor. Copyright © 2003 European Peptide Society
ISSN:1075-2617
DOI:10.1002/psc.527
出版商:John Wiley&Sons, Ltd.
年代:2004
数据来源: WILEY
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5. |
Computational study of the conformational preferences of the (R)‐8‐amino‐pentacyclo[5.4.0.02,6.03,10.05,9] undecane‐8‐carboxylic acid monopeptide |
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Journal of Peptide Science,
Volume 10,
Issue 5,
2004,
Page 274-284
Krishna Bisetty,
Jesus Gomez‐Catalan,
Carlos Aleman,
Ernest Giralt,
Hendrik G. Kruger,
Juan J. Perez,
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摘要:
Abstractα‐Amino acids are important building blocks for the synthesis of a large number of bioactive compounds and pharmaceutical drugs. However, a literature survey revealed that no theoretical conformational study of α‐amino acids with cage carbon frameworks has been performed to date. This paper reports the results of a conformational study on the (R)‐8‐amino‐pentacyclo[5.4.0.02, 6.03,10.05,9] undecane‐8‐carboxylic acid monopeptide (cage monopeptide), using molecular mechanics andab initiomethods. Thein vacuoRamachandran maps computed using the different parameterizations of the AMBER force field show the C7eqstructure as the most favourable conformation, in contrast to the C7axstructure, that is the lowest energy conformation at theab initiolevel. Analysis of these maps reveals the helical preference for the monopeptide and provides the potential for the cage residue to be incorporated into constrained peptide analogues. Copyright © 2003 European Peptide Society and John
ISSN:1075-2617
DOI:10.1002/psc.526
出版商:John Wiley&Sons, Ltd.
年代:2004
数据来源: WILEY
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6. |
New analogues of laminin active fragment YIGSR: synthesis and biological activityin vitroandin vivo |
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Journal of Peptide Science,
Volume 10,
Issue 5,
2004,
Page 285-290
Ewa Witkowska,
Alicja Orłowska,
Jan Izdebski,
Jan Salwa,
Joanna Wietrzyk,
Adam Opolski,
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摘要:
AbstractEleven analogues of the laminin pentapeptide amide fragment Tyr‐Ile‐Gly‐Ser‐Arg‐NH2(YIGSR‐NH2) corresponding to a B1 chain fragment of the glycoprotein laminin have been synthesized by the solid phase method, and their biological activity has been studiedin vitroby a cell adhesion assay: all of them inhibited the adhesion of LLC tumor cells to laminin. The analogues were found to be more resistant to enzymatic degradation in human serum than YIGSR‐NH2itself. Analogue DatIGSHar‐NH2was selected for an experimental pulmonary metastasis assayin vivo: it had higher antimetastatic activity than YIGSR‐NH2. Copyright © 2003 European Peptide Society and Jo
ISSN:1075-2617
DOI:10.1002/psc.537
出版商:John Wiley&Sons, Ltd.
年代:2004
数据来源: WILEY
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7. |
Organization of designed nanofibrils assembled from α‐helical peptides as determined by electron microscopy |
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Journal of Peptide Science,
Volume 10,
Issue 5,
2004,
Page 291-297
Andrey V. Kajava,
Sergey A. Potekhin,
Giampietro Corradin,
Richard D. Leapman,
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摘要:
AbstractSelf‐assembling peptides present attractive platforms for engineering materials with controlled nanostructures. Recently, an α‐helical fibril forming peptide (αFFP) was designed that self‐assembles into nanofibrils at acid pH. Circular dichroism spectroscopy, electron‐microscopy and x‐ray fibre diffraction data showed that the most likely structure of αFFP fibrils is a five‐stranded coiled coil rope. In the present study, scanning transmission electron microscopy (STEM) was used to improve our understanding of the αFFP fibril structure. The measurements of fibril mass per length suggest that there are ten α‐helices in transverse sections of the fibrils. Based on the known data, it is proposed that a predominant fibrillar structure of αFFP is a dimer of α‐helical five‐stranded protofilaments wrapped around a common axis. It is shown that these structures have an axial dimension of 58 ± 16 nm and a width of 4 ± 1 nm. A small number of thin fibrils is also observed in the negative stained preparation and STEM images. The thin fibrils may correspond to the single protofilament. Copyright © 2003 European Peptide Socie
ISSN:1075-2617
DOI:10.1002/psc.520
出版商:John Wiley&Sons, Ltd.
年代:2004
数据来源: WILEY
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8. |
Structure–antiviral activity relationships of cecropin A‐magainin 2 hybrid peptide and its analogues |
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Journal of Peptide Science,
Volume 10,
Issue 5,
2004,
Page 298-303
Dong Gun Lee,
Yoonkyung Park,
Ingnyol Jin,
Kyung‐Soo Hahm,
Hyang‐Hee Lee,
Young‐Hee Moon,
Eun‐Rhan Woo,
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摘要:
AbstractIn order to elucidate the structure–antiviral activity relationship of cecropin A (1–8)‐magainin 2 (1–12) (termed CA‐MA) hybrid peptide, several analogues with amino acid substitutions were synthesized. In a previous study, it was shown that serine at position 16 in CA‐MA hybrid peptide was very important for antimicrobial activity. Analogues were designed to increase the hydrophobic property by substituting a hydrophobic amino acid residue (S→A, V, F or W, position 16) in the CA‐MA hybrid peptide. In this study, the structure–antiviral activity relationships of CA‐MA and its analogues were investigated. In particular, substitution of Ser with a hydrophobic amino acid, Val, Phe or Trp at position 16 caused a dramatic increase in the virus–cell fusion inhibitory activity. These results suggested that the hydrophobicity at position 16 in the hydrophobic region of CA‐MA is important for potent antiviral activity. Copyright © 2003 European Peptide Society
ISSN:1075-2617
DOI:10.1002/psc.504
出版商:John Wiley&Sons, Ltd.
年代:2004
数据来源: WILEY
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9. |
Antinematodal effect of antimicrobial peptide, PMAP‐23, isolated from porcine myeloid againstCaenorhabditis elegans |
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Journal of Peptide Science,
Volume 10,
Issue 5,
2004,
Page 304-311
Yoonkyung Park,
Seung‐Hwan Jang,
Dong Gun Lee,
Kyung‐Soo Hahm,
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摘要:
AbstractThe antinematodal activity and mechanism of a 23‐mer antimicrobial peptide, PMAP‐23, derived from pig myeloid was investigated. PMAP‐23 displayed a strong antinematodal activity against the eggs and worms ofCaenorhabditis elegans. To investigate the antinematodal mechanism of PMAP‐23, fluorescence activated flow cytometry and confocal laser scanning microscopy were performed.C. eleganstreated with PMAP‐23 showed higher fluorescence intensity by propidium iodide (PI) staining than normal cells. Confocal microscopy showed that the peptide was localized in the egg's shell and cell membrane. The action of the peptide againstC. elegansmembranes was examined by testing the membrane disrupting activity using liposome (PC/PS; 3:1, w/w). The result suggests that PMAP‐23 may exert its antinematodal activity by disrupting the structure of the cell membrane via pore formation or via direct interaction with the lipid bilayers. Copyright © 2003 European Peptide Society and John Wil
ISSN:1075-2617
DOI:10.1002/psc.518
出版商:John Wiley&Sons, Ltd.
年代:2004
数据来源: WILEY
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