摘要:

Abstract3‐Substituted‐5‐phenylmorpholinones have been demonstrated to act asN‐protectedC‐terminus activated α‐amino acids capable of undergoing solution phaseN‐terminus peptide extension following standard coupling procedures. TheN‐acylated morpholinones do not undergo epimerisation of the stereocentre of theC‐terminus amino acid residue as oxazolone formation is sterically prevented, althoughC‐terminus peptide coupling is still possible. This convergent approach to peptide synthesis is exemplified by the preparation of L‐ala‐L‐ala‐L‐ala and L‐ala‐D‐ala‐L‐ala. Copyright © 2008 European

ISSN:1075-2617    

DOI:10.1002/psc.1080

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractPreviously, a Myc‐interfering peptide (Mip) was identified for the targeted inactivation of the Myc:Max complex by the combination of rational design and anin vivoprotein‐fragment complementation assay. In the subsequent work presented here, molecular dynamics simulations and free energy calculations based on the molecular mechanics GBSA method were performed to define the contribution of the different amino acids in the Myc:Mip coiled coil domain, and compared to wild‐type Myc:Max. For further optimization of the Myc interference, point mutations were introduced into Mip and analyzed, from which two showed much higher binding affinities in the computational studies in good agreement with the experiment. These mutants with very high potential for inactivation of Myc can now be used as starting point for further optimizations based on the computational as well as experimental protocols presented here. Copyright © 2008 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/psc.1078

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractA strategy was developed to directly assemble 4‐amino‐1,2,4,5‐tetrahydro‐indolo[2,3‐c]‐azepin‐3‐ones on solid‐phase‐supported peptide sequences. Fmoc‐ and Boc‐based strategies were investigated. The Fmoc‐strategy approach strongly depends on the peptide sequence being synthesized while the Boc‐based synthesis leads to excellent results for all the selected peptide analogs. The method was applied to prepare Aia‐analogs of several bioactive peptides containing one or more Trp‐residues which were shown to be important for biological recognition. Copyright © 2008 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.1081

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractAggregation of Aβ peptides is a seminal event in Alzheimer's disease. Detailed understanding of the Aβ assembly process would facilitate the targeting and design of fibrillogenesis inhibitors. Here, conformational studies using FTIR spectroscopy are presented. As a model peptide, the 11–28 fragment of Aβ was used. This model peptide is known to contain the core region responsible for Aβ aggregation. The structural behavior of the peptide during aggregation provoked by the addition of water to Aβ(11–28) solution in hexafluoroisopropanol was compared with the properties of its variants corresponding to natural, clinically relevant mutants at positions 21–23 (A21G, E22K, E22G, E22Q and D23N). The results showed that the aggregation of the peptides proceedsviaa helical intermediate, and it is possible that the formation of α‐helical structures is preceded by creation of 310‐helix/310‐turn structures. Copyright © 2008 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.1085

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractOn consideration that intrinsic structural weakness could affect the segment spanning the α2‐helical residues 173–195 of the PrP, we have investigated the conformational stabilities of some synthetic Ala‐scanned analogs of the peptide derived from the 180–195C‐terminal sequence, using a novel approach whose theoretical basis originates from protein thermodynamics. Even though a quantitative comparison among peptides could not be assessed to rank them according to the effect caused by single amino acid substitution, as a general trend, all peptides invariably showed an appreciable preference for an α‐type organization, consistently with the fact that the wild‐type sequence is organized as an α‐helix in the native protein. Moreover, the substitution of whatever single amino acid in the wild‐type sequence reduced the gap between the α‐ and the β‐propensity, invariably enhancing the latter, but in any case this gap was larger than that evaluated for the full‐length α2‐helix‐derived peptide. It appears that the low β‐conformation propensity of the 180–195 region depends on the simultaneous presence of all of the Ala‐scanned residues, indirectly confirming that theN‐terminal 173–179 segment could play a major role in determining the chameleon conformational behavior of the entire 173–195 region in the PrP. Copyright © 2008 Eu

ISSN:1075-2617    

DOI:10.1002/psc.1086

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractAlthough the N‐terminal region in human apolipoprotein (apo) A‐I is thought to stabilize the lipid‐free structure of the protein, its role in lipid binding is unknown. Using synthetic fragment peptides, we examined the lipid‐binding properties of the first 43 residues (1–43) of apoA‐I in comparison with residues 44–65 and 220–241, which have strong lipid affinity in the molecule. Circular dichroism measurements demonstrated that peptides corresponding to each segment have potential propensity to form α‐helical structure in trifluoroethanol. Spectroscopic and thermodynamic measurements revealed that apoA‐I (1–43) peptide has the strong ability to bind to lipid vesicles and to form α‐helical structure comparable to apoA‐I (220–241) peptide. Substitution of Tyr‐18 located at the center of the most hydrophobic region in residues 1–43 with a helix‐breaking proline resulted in the impaired lipid binding, indicating that the α‐helical structure in this region is required to trigger the lipid binding. In contrast, apoA‐I (44–65) peptide exhibited a lower propensity to form α‐helical structure upon binding to lipid, and apoA‐I (44–65/S55P) peptide exhibited diminished, but not completely impaired, lipid binding, suggesting that the central region of residues 44–65 is not pivotally involved in the formation of the α‐helical structure and lipid binding. These results indicate that the most N‐terminal region of apoA‐I molecule, residues 1–43, contributes to the lipid interaction of apoA‐I through the hydrophobic helical residues. Copy

ISSN:1075-2617    

DOI:10.1002/psc.1092

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractHeparin/heparan sulfate (HS) plays a key role in cellular adhesion. In this study, we utilized a 12‐mer randomEscherichia colicell surface display library to identify the sequence, which binds to heparin. Isolated insert analysis revealed a novel heparin‐binding peptide sequence, VRRSKHGARKDR, designated as HBP12. Our analysis of the sequence alignment of heparin‐binding motifs known as the Cardin–Weintraub consensus (BBXB, where B is a basic residue) indicates that the HBP12 peptide sequence contains two consecutive heparin‐binding motifs (i.e. RRSK and RKDR). SPR‐based BIAcore technology demonstrated that the HBP12 peptide binds to heparin with high affinity (KD= 191 nM). The HBP12 peptide is found to bind the cell surface HS expressed by osteoblastic MC3T3 cells and promote HS‐dependent cell adhesion. Moreover, the surface‐immobilized HBP12 peptide on titanium substrates shows significant increases in the osteoblastic MC3T3‐E1 cell adhesion and proliferation. Copyright © 2008 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.1098

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractWe report here the screening of five marine invertebrate species from two taxa (tunicates and echinoderms) for the presence of cationic antimicrobial peptides (AMP) in defence cells (hemocytes). Antimicrobial activities were detected only in the two tunicatesMicrocosmus sabatieriandHalocynthia papillosa. In addition, we report the isolation and characterization of two novel peptides fromH. papillosahemocytes. These molecules display antibacterial activity against Gram‐positive and Gram‐negative bacteria. Complete peptide characterization was obtained by a combination of Edman degradation and mass spectrometry. The mature molecules, named halocyntin and papillosin, comprise 26 and 34 amino acid residues, respectively. Their primary structure display no significant similarities with previously described AMP. Copyright © 2009 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.1101

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY