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1. |
A general synthetic method toward uridylylated picornavirus VPg proteins |
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Journal of Peptide Science,
Volume 19,
Issue 6,
2013,
Page 333-336
Gerbrand J. Heden van Noort,
Catherine H. Schein,
Herman S. Overkleeft,
Gijsbert A. Marel,
Dmitri V. Filippov,
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摘要:
Small proteins called viral protein genome‐linked (VPg), attached to the 5′‐end of the viral RNA genome are found as common structure in the large family of picornaviruses. The replication of these viruses is primed by this VPg protein linked to a single uridylyl residue. We report a general procedure to obtain such nucleoproteins employing a pre‐uridylylated tyrosine building block in an on‐line solid phase‐based approach. Copyright © 2013 European Peptide Society and John Wil
ISSN:1075-2617
DOI:10.1002/psc.2508
年代:2013
数据来源: WILEY
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2. |
Investigating hydrophobic ligand–receptor interactions in parathyroid hormone receptor using peptide probes |
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Journal of Peptide Science,
Volume 19,
Issue 6,
2013,
Page 337-344
M. E. Cupp,
B. Song,
P. Kibler,
U. S. Raghavender,
S. K. Nayak,
W. Thomsen,
A. K. Galande,
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摘要:
With an increasing number of new chemical entities entering clinical studies, and an increasing share of the market, peptides and peptidomimetics constitute one of the most promising classes of therapeutics. The success of synthetic peptides as therapeutics relies on the lead optimization step in which the lead candidates are modified to improve drug‐like properties of peptides related to potency, pharmacokinetics, solubility, and stability, among others. Peptidomimetics based on theN‐terminal stretch of the first 11 amino acids of the PTH have been investigated as potential lead compounds for the treatment of osteoporosis. On the basis of a peptide reported in the literature, referred to here as the Parent Peptide (H‐Aib‐Val‐Aib‐Glu‐Ile‐Gln‐Leu‐Nle‐His‐Gln‐Har‐NH2), we conducted systematic SAR analyses to investigate the effects of altering peptide hydrophobicity on PTH receptor functional potency as measured by the cAMP (cyclic adenosine monophosphate) accumulation andβ‐arrestin recruitment assays. Among hydrophobic residues, we found that the Val2 position shows the least flexibility in terms of the SAR studies, whereas the Leu7 position appeared to be most flexible. Through circular dichroism and nuclear magnetic resonance spectroscopy studies, we were able to establish that changes in hydrophobic residues significantly change the extent of peptide helicity and that the helical character correlates well with receptor agonist activity. Here, we report several novel PTH 1–11 peptidomimetics that show comparable or enhanced potency to stimulate Gs‐signaling overβ‐arrestin recruitment as compared with such properties of PTH 1–34 and the Parent Peptide. Copyright © 2013 European
ISSN:1075-2617
DOI:10.1002/psc.2502
年代:2013
数据来源: WILEY
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3. |
Theβ‐sheet breakers and π‐stacking |
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Journal of Peptide Science,
Volume 19,
Issue 6,
2013,
Page 345-349
Adam Jarmuła,
Dariusz Stępkowski,
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摘要:
Fibrillation ofβ‐amyloid is recognized as a key process leading to the development of Alzheimer's disease. Small peptides calledβ‐sheet breakers were found to inhibit the process ofβ‐amyloid fibrillation and to dissolve amyloid fibrilsin vitro,in vivo, and in cell culture studies [1,2]. The mechanism by which peptide inhibition takes place remains elusive and a detailed model needs to be established. Here, we present new insights into the possible role of consecutive Phe residues, present in the structure ofβ‐sheet breakers, supported by the results obtained by means of MD simulations. We performed a 30‐ns MD of twoβ‐sheet breakers: iAβ5 (LPFFD) and iAβ6 (LPFFFD) which have two and three consecutive Phe residues, respectively. We have found that Phe rings in these peptides tend to form stacked conformations. For one of the peptides – iAβ6 – the calculated electrostatic contribution to free energy of one of the conformers with three rings stacked (c2) is significantly lower than that corresponding to the unstacked one (c1), two rings stacked (c0) and second conformer with three rings stacked (c3). This may favor the interaction of the c2 conformer with the target on amyloid fibril. We hypothesize that the mechanism of inhibition of amyloidogenesis byβ‐sheet breaker involves competition among π‐stacked Phe residues of the inhibitor and π‐stacking within theβ‐amyloid fibril. iAβ6 may be a promising candidate for a lead compound of amyloidogenesis inhibitors. Copyright © 2013 European Pep
ISSN:1075-2617
DOI:10.1002/psc.2506
年代:2013
数据来源: WILEY
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4. |
A convenient method for europium‐labeling of a recombinant chimeric relaxin family peptide R3/I5 for receptor‐binding assays |
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Journal of Peptide Science,
Volume 19,
Issue 6,
2013,
Page 350-354
Wei‐Jie Zhang,
Qian Jiang,
Xin‐Yi Wang,
Ge Song,
Xiao‐Xia Shao,
Zhan‐Yun Guo,
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摘要:
Relaxin family peptides have important biological functions, and so far, four G‐protein‐coupled receptors have been identified as their receptors (RXFP1–4). A chimeric relaxin family peptide R3/I5, containing the B‐chain of relaxin‐3 and the A‐chain of INSL5, is a selective agonist for both RXFP3 and RXFP4. In a previous study, europium‐labeled R3/I5, as a nonradioactive and low‐background receptor‐binding tracer, was prepared through a chemical synthesis approach. In the present study, we established a convenient alternative approach for preparing the europium‐labeled R3/I5 tracer based on a recombinant R3/I5 designed to carry a solubilizing tag at the A‐chain N‐terminus and a pyroglutamate residue at the B‐chain N‐terminus. Because of the presence of a single primary amine moiety, the recombinant R3/I5 peptide was site‐specifically mono‐labeled at the A‐chain N‐terminus by a diethylenetriaminepentaacetic acid/europium moiety through a convenient one‐step procedure. The diethylenetriaminepentaacetic acid/Eu3+‐labeled R3/I5 bound both receptors RXFP3 and RXFP4 with high binding affinities and low nonspecific binding. Thus, we have presented a valuable nonradioactive tracer for future interaction studies on RXFP3 and RXFP4 with various natural or designed ligands. The present approach could also be adapted for preparing and labeling of other chimeric relaxin family peptides. Copyright © 2013 European
ISSN:1075-2617
DOI:10.1002/psc.2507
年代:2013
数据来源: WILEY
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5. |
Endothelins specifically recognize lysophosphatidylcholine micelles |
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Journal of Peptide Science,
Volume 19,
Issue 6,
2013,
Page 355-361
Akira Sato,
Keiichi Ebina,
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摘要:
Lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low‐density lipoprotein (ox‐LDL), is implicated in numerous inflammatory diseases, including atherosclerosis. Here, to clarify the relationship between bioactive endothelins (ETs) (which are considered to be potent proinflammatory mediators) and LPC/ox‐LDL, we investigated the interaction between ETs and LPC/ox‐LDL by fluorescence spectroscopy and western blotting. Tryptophan fluorescence measurements revealed ETs specifically interacted with LPC at concentrations that exceeded the critical micelle concentration (CMC). The tryptophan residue in ETs was not likely to be involved directly in the interaction between ETs and LPC micelles. Tryptophan fluorescence quenching revealed tryptophan residue in ETs where LPC concentrations were below the CMC may be buried deeply in the peptide or may interact with other amino acid residues, whereas tryptophan residue in ETs in the presence of LPC at concentrations exceeding the CMC was exposed outside of the peptide. Furthermore, ETs bind to ox‐LDL in a concentration‐dependent manner. These results strongly suggest that ox‐LDL contains micelle‐rich LPCs and that ETs specifically interact with the bioactive LPC micelles. Further study of the interaction between ETs and LPC micelles contained in ox‐LDL will provide important information on the development and progression of many inflammatory diseases, including atherosclerosis. Copyright © 2013 European Peptide Society and Jo
ISSN:1075-2617
DOI:10.1002/psc.2509
年代:2013
数据来源: WILEY
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6. |
Identification and characterization of peptides that bind the PPIase domain of Parvulin17 |
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Journal of Peptide Science,
Volume 19,
Issue 6,
2013,
Page 362-369
Imadeldin Elfaki,
Andre Knitsch,
Anja Matena,
Peter Bayer,
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摘要:
Peptidyl‐prolylcis‐transisomerases (PPIases) are the enzymes that increase the rate of isomerization of the peptide bondN‐terminal to the proline substrate. Par14 and its isoform Par17 belong to the Parvulin family of PPIases. Par14 can bind AT‐rich double‐stranded DNA and was shown to be part of the pre‐ribosomal ribonucleoprotein (pre‐rRNP) complexes, where it functions as an RNA processing factor that is involved in ribosome biogenesis. Its longer isoform Par17 is expressed only in cells of hominids, where it is targeted to the mitochondria. To find binding partners (peptides or proteins) for Par17, we applied the phage display technology. We panned 7‐mer and 12‐mer peptide libraries against Par17. The consensus sequence XHSXVHØ, where X can be any amino acid and Ø is a hydrophobic amino acid, was enriched from both libraries. We demonstrate the binding of this motif to the PPIase domain of Par17 using phage ELISA and NMR spectroscopy. We propose that residues Met90, Val91, Phe94, Gln95, Glu96, and Ala98 of Par17 are involved in substrate recognition, and that the phage display‐selected motif XHSXVHØ can be recognized by Par17 PPIase domainin vivo. Copyright © 2013 European Peptide Society a
ISSN:1075-2617
DOI:10.1002/psc.2510
年代:2013
数据来源: WILEY
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7. |
New m‐calpain substrate‐based azapeptide inhibitors |
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Journal of Peptide Science,
Volume 19,
Issue 6,
2013,
Page 370-376
Zoltán Bánóczi,
Ágnes Tantos,
Attila Farkas,
Zsuzsa Majer,
Levente E. Dókus,
Péter Tompa,
Ferenc Hudecz,
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摘要:
Calpains are intracellular cysteine proteases with several important physiological functions. Calpain inhibitors may be promising tools in the analysis of the function of the enzyme in diseases caused by overexpression/activation. Here, we report on the synthesis, solution conformation, and characterization of novel group of azapeptides whose sequences originate from an efficient m‐calpain substrate, TPLKSPPPSPR, described by us earlier and possess varying levels of calpain inhibition. The Lys residue at P1position was replaced with azaglycine (NH2‐NH‐COOH) and further changes were made as follows: theN‐terminal or/andC‐terminal were truncated, amino acids were also changed at P3, P2, P′1, or P′2positions. Our results indicate that the identity of amino acid moieties between P4and P′5positions is essential for the inhibitory activity. Only changes at position P3(Pro) are tolerated. Azapeptide analogs, described in this communication could be considered as useful set of compounds for elucidation of the enzyme interaction at P and P′ sites. Copyright © 2013 European Peptide Society and Jo
ISSN:1075-2617
DOI:10.1002/psc.2511
年代:2013
数据来源: WILEY
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8. |
Nisin adsorption on hydrophilic and hydrophobic surfaces: evidence of its interactions and antibacterial activity |
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Journal of Peptide Science,
Volume 19,
Issue 6,
2013,
Page 377-385
Layal Karam,
Charafeddine Jama,
Nicolas Nuns,
Anne‐Sophie Mamede,
Pascal Dhulster,
Nour‐Eddine Chihib,
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摘要:
Study of peptides adsorption on surfaces remains a current challenge in literature. A complementary approach, combining X‐ray photoelectron spectroscopy (XPS) and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) was used to investigate the antimicrobial peptide nisin adsorption on hydrophilic and hydrophobic surfaces. The native low density polyethylene was used as hydrophobic support and it was grafted with acrylic acid to render it hydrophilic. XPS permitted to confirm nisin adsorption and to determine its amount on the surfaces. ToF‐SIMS permitted to identify the adsorbed bacteriocin type and to observe its distribution and orientation behavior on both types of surfaces. Nisin was more oriented by its hydrophobic side to the hydrophobic substrate and by its hydrophilic side to the outer layers of the adsorbed peptide, in contrast to what was observed on the hydrophilic substrate. A correlation was found between XPS and ToF‐SIMS results, the types of interactions on both surfaces and the observed antibacterial activity. Such interfacial studies are crucial for better understanding the peptides interactions and adsorption on surfaces and must be considered when setting up antimicrobial surfaces. Copyright © 2013 European Peptide Society and John Wil
ISSN:1075-2617
DOI:10.1002/psc.2512
年代:2013
数据来源: WILEY
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9. |
Effect of agitation on the peptide fibrillization: Alzheimer's amyloid‐βpeptide 1‐42 but not amylin and insulin fibrils can grow under quiescent conditions |
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Journal of Peptide Science,
Volume 19,
Issue 6,
2013,
Page 386-391
Ann Tiiman,
Andra Noormägi,
Merlin Friedemann,
Jekaterina Krishtal,
Peep Palumaa,
Vello Tõugu,
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摘要:
Many peptides and proteins can form fibrillar aggregatesin vitro, but only a limited number of them are forming pathological amyloid structures in vivo. We studied the fibrillization of four peptides – Alzheimer's amyloid‐β(Aβ) 1‐40 and 1‐42, amylin and insulin. In all cases, intensive mechanical agitation of the solution initiated fast fibrillization. However, when the mixing was stopped during the fibril growth phase, the fibrillization of amylin and insulin was practically stopped, and the rate for Aβ40substantially decreased, whereas the fibrillization of Aβ42peptide continued to proceed with almost the same rate as in the agitated conditions. The reason for the different sensitivity of thein vitrofibrillization of these peptides towards agitation in the fibril growth phase remains elusive. Copyright © 2013 European Peptide Society and John W
ISSN:1075-2617
DOI:10.1002/psc.2513
年代:2013
数据来源: WILEY
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