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1. |
In vitromodels for metabolic studies of small peptide hormones in sport drug testing |
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Journal of Peptide Science,
Volume 21,
Issue 1,
2015,
Page 1-9
Simone Esposito,
Koen Deventer,
Lore Geldof,
Peter Van Eenoo,
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摘要:
Peptide hormones represent an emerging class of potential doping agents. Detection of their misuse is difficult due to their short half‐life in plasma and rapid elimination. Therefore, investigating their metabolism can improve detectability. Unfortunately, pharmacokinetic studies with human volunteers are often not allowed because of ethical constraints, and therefore alternative models are needed. This study was performed in order to evaluatein vitromodels (human liver microsomes and S9 fraction) for the prediction of the metabolism of peptidic doping agents and to compare them with the established models. The peptides that were investigated include desmopressin, TB‐500, GHRP‐2, GHRP‐6, hexarelin, LHRH and leuprolide. Several metabolites were detected for each peptide after incubation with human liver microsomes, S9 fraction, and serum, which all showed endopeptidase and exopeptidase activity.In vitromodels from different organs (liver vs. kidney) were compared, but no significant differences were recorded. Deamidation was not observed in any of the models and was therefore evaluated by incubation with α‐chymotrypsin.In conclusion,in vitromodels are useful tools for forensic and clinical analysts to detect peptidic metabolic markers in biological fluids. Copyright © 2014 European Peptide Society and John Wile
ISSN:1075-2617
DOI:10.1002/psc.2710
年代:2015
数据来源: WILEY
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2. |
Computational prediction of anti HIV‐1 peptides andin vitroevaluation of anti HIV‐1 activity of HIV‐1 P24‐derived peptides |
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Journal of Peptide Science,
Volume 21,
Issue 1,
2015,
Page 10-16
Naghmeh Poorinmohammad,
Hassan Mohabatkar,
Mandana Behbahani,
Davood Biria,
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摘要:
The world is entering the third decade of the acquired immunodeficiency syndrome (AIDS) pandemic. The primary cause of the disease has known to be human immunodeficiency virus type I (HIV‐1). Recently, peptides are shown to have high potency as drugs in the treatment of AIDS. Therefore, in the present study, we have developed a method to predict anti‐HIV‐1 peptides using support vector machine (SVM) as a powerful machine learning algorithm. Peptide descriptors were represented based on the concept of Chou's pseudo‐amino acid composition (PseAAC). HIV‐1 P24‐derived peptides were examined to predict anti‐HIV‐1 activity among them. The efficacy of the prediction was then validatedin vitro. The mutagenic effect of validated anti‐HIV‐1 peptides was further investigated by the Ames test. Computational classification using SVM showed the accuracy and sensitivity of 96.76% and 98.1%, respectively. Based on SVM classification algorithm, 3 out of 22 P24‐derived peptides were predicted to be anti‐HIV‐1, while the rest were estimated to be inactive. HIV‐1 replication was inhibited by the three predicted anti‐HIV‐1 peptides as revealedin vitro, while the results of the same test on two of non‐anti‐HIV‐1 peptides showed complete inactivity. The three anti‐HIV‐1 peptides were shown to be not mutagenic because of the Ames test results. These data suggest that the proposed computational method is highly efficient for predicting the anti‐HIV‐1 activity of any unknown peptide having only its amino acid sequence. Moreover, further experimental studies can be performed on the mentioned peptides, which may lead to new anti‐HIV‐1 peptide therapeutics candidates. Copyright © 2014
ISSN:1075-2617
DOI:10.1002/psc.2712
年代:2015
数据来源: WILEY
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3. |
Peptide backbone cleavage byα‐amidation is enhanced at methionine residues |
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Journal of Peptide Science,
Volume 21,
Issue 1,
2015,
Page 17-23
Michael Hellwig,
Katja Löbmann,
Tom Orywol,
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摘要:
Cleavage reactions at backbone loci are one of the consequences of oxidation of proteins and peptides. Duringα‐amidation, the Cα–N bond in the backbone is cleaved under formation of an N‐terminal peptide amide and a C‐terminal keto acyl peptide. On the basis of earlier works, a facilitation ofα‐amidation by the thioether group of adjacent methionine side chains was proposed. This reaction was characterized by using benzoyl methionine and benzoyl alanyl methionine as peptide models. The decomposition of benzoylated amino acids (benzoyl‐methionine, benzoyl‐alanine, and benzoyl‐methionine sulfoxide) to benzamide in the presence of different carbohydrate compounds (reducing sugars, Amadori products, and reductones) was studied during incubation for up to 48 h at 80 °C in acetate‐buffered solution (pH 6.0). Small amounts of benzamide (0.3–1.5 mol%) were formed in the presence of all sugars and from all benzoylated species. However, benzamide formation was strongly enhanced, when benzoyl methionine was incubated in the presence of reductones and Amadori compounds (3.5–4.2 mol%). The reaction was found to be intramolecular, becauseα‐amidation of a similar 4‐methylbenzoylated amino acid was not enhanced in the presence of benzoyl‐methionine and carbohydrate compounds. In the peptide benzoyl‐alanyl‐methionine,α‐amidation at the methionine residue is preferred overα‐amidation at the benzoyl peptide bond. We propose here a mechanism for the enhancement ofα‐amidation at methionine residues. Copyright ©
ISSN:1075-2617
DOI:10.1002/psc.2713
年代:2015
数据来源: WILEY
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4. |
Angiotensin II restricted analogs with biological activity in the erythrocytic cycle ofPlasmodium falciparum |
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Journal of Peptide Science,
Volume 21,
Issue 1,
2015,
Page 24-28
Marcelo Der Torossian Torres,
Adriana Farias Silva,
Leandro Silva,
Ana Acácia Pinheiro,
Vani Xavier Jr. Oliveira,
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摘要:
The anti‐plasmodial activity of conformationally restricted analogs of angiotensin II againstPlasmodium gallinaceumhas been described. To observe activity against anotherPlasmodiumspecies, invasion of red blood cells byPlasmodium falciparumwas analyzed. Analogs restricted with lactam or disulfide bridges were synthesized to determine their effects and constraints in the peptide–parasite interaction. The analogs were synthesized usingtert‐butoxycarbonyl and fluoromethoxycarbonyl solid phase methods, purified by liquid chromatography, and characterized by mass spectrometry.Results indicated that the lactam bridge restricted analogs 1 (Glu‐Asp‐Arg‐Orn‐Val‐Tyr‐Ile‐His‐Pro‐Phe) and 3 (Asp‐Glu‐Arg‐Val‐Orn‐Tyr‐Ile‐His‐Pro‐Phe) showed activity toward inhibition of ring formation stage ofP. falciparumerythrocytic cycle, preventing invasion in about 40% of the erythrocytes. The disulfide‐bridged analog 10 (Cys‐Asp‐Arg‐Cys‐Val‐Tyr‐Ile‐His‐Pro‐Phe) was less effective yet significant, showing a 25% decrease in infection of new erythrocytes. In all cases, the peptides presented no pressor activity, and hydrophobic interactions between the aromatic and alkyl amino acid side chains were preserved, a factor proven important in efficacy againstP. gallinaceum. In contrast, hydrophilic interactions between the Asp1carboxyl and Arg2guanidyl groups proved not to be as important as they were in the case ofP. gallinaceum,while interactions between the Arg2guanidyl and Tyr4hydroxyl groups were not important in either case. The β‐turn conformation was predominant in all of the active peptides, proving importance in anti‐plasmodial activity. This approach provides insight for understanding the importance of each amino acid residue on the native angiotensin II structure and a new direction for the design of potential chemotherapeutic agents.
ISSN:1075-2617
DOI:10.1002/psc.2714
年代:2015
数据来源: WILEY
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5. |
Novel M‐Superfamily and T‐Superfamily conotoxins and contryphans from the vermivorous snailConus figulinus |
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Journal of Peptide Science,
Volume 21,
Issue 1,
2015,
Page 29-39
Rajaian Pushpabai Rajesh,
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摘要:
The venom ofConus figulinus, a vermivorous cone snail, found in the south east coast of India, has been studied in an effort to identify novel peptide toxins. The amino acid sequences of seven peptides have been established usingde novomass spectrometric based sequencing methods. Among these, three peptides belong to the M‐Superfamily conotoxins, namely, Fi3a, Fi3b, and Fi3c, and one that belongs to the T‐Superfamily, namely, Fi5a. The other three peptides are contryphans, namely, contryphans fib, fic, and fid. Of these Fi3b, Fi3c, Fi5a, and contryphan fib are novel and are reported for the first time from venom ofC. figulinus. The details of the sequencing methods and the relationship of these peptides with other ‘M’‐Superfamily conotoxins from the fish hunting and mollusk hunting clades are discussed. These novel peptides could serve as a lead compounds for the development of neuropharmacologically important drugs. Copyright © 2014 European Peptide Society and John Wil
ISSN:1075-2617
DOI:10.1002/psc.2715
年代:2015
数据来源: WILEY
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6. |
A simple protocol for combinatorial cyclic depsipeptide libraries sequencing by matrix‐assisted laser desorption/ionisation mass spectrometry |
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Journal of Peptide Science,
Volume 21,
Issue 1,
2015,
Page 40-45
Juan M. Gurevich‐Messina,
Silvana L. Giudicessi,
María C. Martínez‐Ceron,
Gerardo Acosta,
Rosa Erra‐Balsells,
Osvaldo Cascone,
Fernando Albericio,
Silvia A. Camperi,
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摘要:
Short cyclic peptides have a great interest in therapeutic, diagnostic and affinity chromatography applications. The screening of ‘one‐bead‐one‐peptide’ combinatorial libraries combined with mass spectrometry (MS) is an excellent tool to find peptides with affinity for any target protein. The fragmentation patterns of cyclic peptides are quite more complex than those of their linear counterparts, and the elucidation of the resulting tandem mass spectra is rather more difficult. Here, we propose a simple protocol for combinatorial cyclic libraries synthesis and ring opening before MS analysis. In this strategy, 4‐hydroxymethylbenzoic acid, which forms a benzyl ester with the first amino acid, was used as the linker. A glycolamidic ester group was incorporated after the combinatorial positions by adding glycolic acid. The library synthesis protocol consisted in the following: (i) incorporation of Fmoc‐Asp[2‐phenylisopropyl (OPp)]‐OH to Ala‐Gly‐oxymethylbenzamide‐ChemMatrix, (ii) synthesis of the combinatorial library, (iii) assembly of a glycolic acid, (iv) couple of an Ala residue in theN‐terminal, (v) removal of OPp, (vi) peptide cyclisation through side chain Asp andN‐Ala amino terminus and (vii) removal of side chain protecting groups. In order to simultaneously open the ring and release each peptide, benzyl and glycolamidic esters were cleaved with ammonia. Peptide sequences could be deduced from the tandem mass spectra of each single bead evaluated. The strategy herein proposed is suitable for the preparation of one‐bead‐one‐cyclic depsipeptide libraries that can be easily open for its sequencing by matrix‐assisted laser desorption/ionisation MS. It employs techniques and reagents frequently used in a broad range of laboratories without special expertise in organic synthesis. Copyright © 2014 European Pept
ISSN:1075-2617
DOI:10.1002/psc.2716
年代:2015
数据来源: WILEY
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7. |
Prokaryotic expression and antimicrobial mechanism of XPF‐St7‐derived α‐helical peptides |
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Journal of Peptide Science,
Volume 21,
Issue 1,
2015,
Page 46-52
Tonghui Yi,
Yibing Huang,
Yuxin Chen,
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摘要:
XPF‐St7 (GLLSNVAGLLKQFAKGGVNAVLNPK) is an antimicrobial peptide isolated fromSilurana tropicalis. We developed an α‐helical segment of XPF‐St7 termed as XPF2. Using the XPF2 as a framework, we increased the positive net charge of XPF2 by amino acid substitutions, and thus obtained two novel antimicrobial peptides XPF4 and XPF6. These were each fused with an ubiquitin tag and successfully expressed inEscherichia coli. This ubiquitin fusion system may present a viable alternative for industrial production of antimicrobial peptides. XPF4 and XPF6 showed much better overall antimicrobial activity against both Gram‐negative and Gram‐positive bacteria than XPF2. The therapeutic index of XPF4 and XPF6 was 5.6‐fold and 6.7‐fold of XPF2, respectively. Bacterial cell membrane permeabilization and genomic DNA interaction assays were utilized to explore the mechanism of action of XPF serial peptides. The results revealed that the target of these antimicrobial peptides was the bacterial cytoplasmic membrane. Copyright © 2014 European Peptide Society and John
ISSN:1075-2617
DOI:10.1002/psc.2722
年代:2015
数据来源: WILEY
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8. |
Fmoc‐Sec(Xan)‐OH: synthesis and utility of Fmoc selenocysteine SPPS derivatives with acid‐labile sidechain protection |
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Journal of Peptide Science,
Volume 21,
Issue 1,
2015,
Page 53-59
Stevenson Flemer,
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摘要:
AbstractWe report here the synthesis of the first selenocysteine SPPS derivatives which bear TFA‐labile sidechain protecting groups. New compounds Fmoc‐Sec(Xan)‐OH and Fmoc‐Sec(Trt)‐OH are presented as useful and practical alternatives to the traditional Fmoc‐Sec‐OH derivatives currently available to the peptide chemist. From abisFmoc‐protected selenocystine precursor, multiple avenues of diselenide reduction were attempted to determine the most effective method for subsequent attachment of the protecting group electrophiles. Our previously reported one‐pot reduction methodology was ultimately chosen as the optimal approach toward the synthesis of these novel building blocks, and both were easily obtained in high yield and purity. Fmoc‐Sec(Xan)‐OH was discovered to be bench‐stable for extended timeframes while the corresponding Fmoc‐Sec(Trt)‐OH derivative appeared to detritylate slowly when not stored at −20 °C. Both Sec derivatives were incorporated into single‐ and multiple‐Sec‐containing test peptides in order to ascertain the peptides' deprotection behavior and final form upon TFA cleavage. Single‐Sec‐containing test peptides were always isolated as their corresponding diselenide dimers, while dual‐Sec‐containing peptide sequences were afforded exclusively as their intramolecular diselenides. Copyright © 2014 Eu
ISSN:1075-2617
DOI:10.1002/psc.2723
年代:2015
数据来源: WILEY
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9. |
Issue information |
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Journal of Peptide Science,
Volume 21,
Issue 1,
2015,
Page -
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ISSN:1075-2617
DOI:10.1002/psc.2690
年代:2015
数据来源: WILEY
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