摘要:

Of all the commercially available amino acid derivatives for solid phase peptide synthesis, none has a greater abundance of side‐chain protection diversity than cysteine. The high reactivity of the cysteine thiol necessitates its attenuation during peptide construction. Moreover, the propensity of cysteine residues within a peptide or protein sequence to form disulfide connectivity allows the opportunity for the peptide chemist to install these disulfides iteratively as a post‐synthetic manipulation through the judicious placement of orthogonal pairs of cysteine S‐protection within the peptide's architecture. It is important to continuously discover new vectors of deprotection for these different blocking protocols in order to achieve the highest degree of orthogonality between the removal of one species in the presence of another. We report here a complete investigation of the scope and limitations of the deprotective potential of 2,2′‐dithiobis(5‐nitropyridine) (DTNP) on a selection of commercially available Cys S‐protecting groups. The gentle conditions of DTNP in a TFA solvent system show a remarkable ability to deprotect some cysteine blocking functionality traditionally removable only by more harsh or forcing conditions. Beyond illustrating the deprotective ability of this reagent cocktail within a cysteine‐containing peptide sequence, the utility of this method was further demonstrated through iterative disulfide formation in oxytocin and apamin test peptides. It is shown that this methodology has high potential as a stand‐alone cysteine deprotection technique or in further manipulation of disulfide architecture within a more complex cysteine‐containing peptide template. Copyright © 2011 European Peptide Society and

ISSN:1075-2617    

DOI:10.1002/psc.1403

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

In this study, two novel antimicrobial peptides from the skin secretions of the marsh frog,Rana ridibunda, named temporin‐Ra and temporin‐Rb, were identified and purified using RP‐HPLC. Temporin‐Ra and temporin‐Rb are composed of 14 and 12 amino acids, respectively. Our results show that these peptides have inhibitory effects on both gram‐negative and gram‐positive bacteria, especially antibiotic resistant strains prevalent in hospitals, such asStaphylococcus aureusandStreptococcus agalactiae. The sequences and molecular weights of these peptides were determined using tandem MS. The molecular masses were found to be 1242.5 Da for temporin‐Rb and 1585.1 Da for temporin‐Ra. Human red blood cells tolerated well exposure to temporin‐Ra and temporin‐Rb, which, at a concentration of 60 µg/ml, induced 1.3% and 1.1% hemolysis, respectively. MIC values of these peptides are suitable for potent antimicrobial peptides. The low hemolytic effect and wide‐spectrum antimicrobial activity suggest a possible therapeutic application of these novel peptides. Copyright © 2011 European Peptide S

ISSN:1075-2617    

DOI:10.1002/psc.1409

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

We extended the use of Peplook, an in silico procedure for the prediction of three‐dimensional (3D) models of linear peptides to the prediction of 3D models of cyclic peptides and thanks to theab initiocalculation procedure, to the calculation of peptides with non‐proteinogenic amino acids. Indeed, such peptides cannot be predicted by homology or threading. We compare the calculated models with NMR and X‐ray models and for the cyclic peptides, with models predicted by other in silico procedures (Pep‐Fold and I‐Tasser). For cyclic peptides, on a set of 38 peptides, average root mean square deviation of backbone atoms (BB‐RMSD) was 3.8 and 4.1 Å for Peplook and Pep‐Fold, respectively. The best results are obtained with I‐Tasser (2.5 Å) although evaluations were biased by the fact that the resolved Protein Data Bank models could be used as template by the server. Peplook and Pep‐Fold give similar results, better for short (up to 20 residues) than for longer peptides. For peptides with non‐proteinogenic residues, performances of Peplook are sound with an average BB‐RMSD of 3.6 Å for ‘non‐natural peptides’ and 3.4 Å for peptides combining non‐proteinogenic residues and cyclic structure. These results open interesting possibilities for the design of peptidic drugs. Copyright © 2011 Europea

ISSN:1075-2617    

DOI:10.1002/psc.1410

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

No abstract is available for this article.

ISSN:1075-2617    

DOI:10.1002/psc.2446

年代:2012

数据来源: WILEY

摘要:

No abstract is available for this article.

ISSN:1075-2617    

DOI:10.1002/psc.2447

年代:2012

数据来源: WILEY

摘要:

IL‐15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL‐15 antagonist peptide corresponding to sequence 36–45 of IL‐15 (KVTAMKCFLL) named P8, which specifically binds to IL‐15Rαand inhibits IL‐15 biological activity with a half maximal inhibitory concentration (IC50) of 130 µmin CTLL‐2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL‐15Rα, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL‐15Rα. We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non‐charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24 µm. We also found that this peptide was more active than peptide P8 in the inhibition of TNFαsecretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL‐15 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis. Copyright © 2011 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.1411

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

No abstract is available for this article.

ISSN:1075-2617    

DOI:10.1002/psc.2448

年代:2012

数据来源: WILEY

摘要:

A methodology is presented for the facile synthesis of Arg‐containing peptides modified at the guanidine headgroup as substituted amidine cores. This process allows for the iterative construction of these Arg isosteres while the peptide is being built out on the solid support, providing a high potential for diversity in substitution pattern in the resulting peptide. A series ofN‐Pmc‐substituted thioamides were condensed with deprotected δ‐NOrn‐bearing peptides while attached to the solid support using Mukaiyama's reagent as coupling reagent, yielding isosteric Arg‐containing analogs. Peptides were cleaved using trimethylsilyl trifluoromethanesulfonate/TFA and analyzed in their crude form in order to illustrate the amenability of this process toward production of peptide isolates in high crude purity. Arg‐containing peptides having a single Arg isostere were utilized to show the general utility of this approach as well as a multiple‐Arg‐containing construct, illustrating the amenability of this method toward stepwise construction of differently substituted amidine headgroups within the same peptide. Copyright © 2011 European Peptide Society and J

ISSN:1075-2617    

DOI:10.1002/psc.1412

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

A set of analogues of the 14‐residue peptaibol tylopeptin B, containing the stable free‐radical 4‐amino‐1‐oxyl‐2,2,6,6,‐tetramethylpiperidine‐4‐carboxylic acid (TOAC) at one or two selected positions, was synthesized by the solid‐phase methodology. A solution conformational analysis performed by FTIR absorption and CD suggests that, in membrane‐mimicking solvents, the labeled tylopeptin B analogues preserve the helical propensity of the parent peptide, with a preference for theα‐helix or the 310‐helix type depending upon the nature of the solvent. In aqueous environment, the spin‐labeled analogues present a higher content of helical conformation as a consequence of the strong helix promoter effect of the conformationally constrained TOAC residue. We observed a progressive increase of the quenching effect of the nitroxyl radical on the fluorescence of theN‐terminal tryptophan as TOAC replaces the Aib residue at positions 13, 8, and 4, respectively. A membrane permeabilization assay performed on two selected analogues, TOAC8‐ and TOAC13‐tylopeptin B, showed that the labeled peptides exhibit membrane‐modifying properties comparable with those of the natural peptaibiotic. We conclude that our TOAC paramagnetic analogues of tylopeptin B are good models for a detailed ESR investigation of the mechanism of membrane permeabilization induced by medium‐length peptaibiotics. Copyright © 2011 European P

ISSN:1075-2617    

DOI:10.1002/psc.1413

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY

摘要:

Slc11a1 is an integral membrane protein with 12 putative transmembrane domains (TMDs) and functions as a pH‐coupled divalent metal cation transporter. The conservation of three negatively charged residues in the TMD3 of Slc11 protein family implies the important role of this domain in the function of the proteins. However, aggregation of the transmembrane peptide in micelles prevents structural study of the peptide in these membrane‐mimetic environments by NMR spectroscopy. Here, we characterized the structure, position, and assembly model of Slc11a1‐TMD3 (Lys128‐Ile151) in SDS micelles by the NMR study of its Leu‐substituted peptide. It was found that the two‐site substitutions of Ala for Leu residues at positions 136 and 140 of TMD3 disrupt the aggregation without altering the secondary structure of the peptide. The Leu‐substituted peptide folds as anα‐helix spanning from Leu133 to Gly144 and embedded in the micelles. A Leu zipper is suggested to account for the self‐assembly of the wild‐type peptide in SDS micelles. Copyright © 2011 European Peptide Society and

ISSN:1075-2617    

DOI:10.1002/psc.1414

出版商:John Wiley&Sons, Ltd    

年代:2012

数据来源: WILEY