摘要:

AbstractThe influence of the two histidine and two arginine residues of mast cell degranulating peptide (MCD) in activity and binding was studied by replacing these amino acids in the MCD sequence withL‐alanine. Their histamine releasing activity was determined on rat peritoneal mast cells. Their binding affinity to the FcεRIα binding subunit of the human mast cell receptor protein, was carried out using fluorescence polarization. The histamine assay showed that replacement of His13by Ala occurred without loss of activity compared with the activity of MCD. Alanine substitutions for Arg7and His8resulted in an approximately 40‐fold increase, and for Arg16in a 14‐fold increase in histamine‐releasing activity of MCD. The binding affinities of the analogs were tested by competitive displacement of bound fluorescent MCD peptide from the FcεRIα binding protein of the mast cell receptor by the Ala analogs using fluorescence polarization. The analogs Ala8(for His) and Ala16(for Arg) showed the same binding affinities as MCD, whereas analog Ala7(for Arg) and analog Ala13(for His) showed slightly better binding affinity than the parent compound. This study showed that the introduction of alanine residues in these positions resulted in MCD agonists of diverse potency. These findings will be useful in further MCD structure–activity studies. Copyright © 2004 European Peptide Society and John W

ISSN:1075-2617    

DOI:10.1002/psc.532

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractA solid‐phase approach was used to prepare 20 cystine amide derivatives with disulfide bond formation resulting from an intra‐site reaction between neighbouring cysteine residues. Library members were screened as potential organogelators in a range of solvent mixtures and resulted in the identification of a potent gelator able to rigidify water/DMSO mixtures at concentrations as low as 1.3 mM. Copyright © 2004 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.544

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractAnchoring an α‐amino acid residue by its amine function onto a solid support is an alternative to develop chemistry on its carboxylic function. This strategy can involve the use of amino‐acid esters as precursors of the carboxylic function. A complete study on the Wang‐resin was performed to determine the non‐racemizing saponification conditions of anchored α‐amino esters. The use of LiOH, NaOH, NaOSi(Me)3, various solvents and temperatures were tested for this reaction. After saponification and cleavage from the support, samples were examined through their Marfey's derivatives by reversed phase HPLC to evaluate the percentage of racemization. Copyright © 2004 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.561

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractThe antibacterial activity againstEscherichia coliandStaphylococcus aureushas been studied for a number of modified pentadecapeptides based on lactoferricins of different origin. The peptides were classified by multivariate methods and quantitative structure–activity relationships (QSAR) were developed using theoretically derived variables for the amino acids. For the modified peptides based on bovine lactoferricin (LFB) a model was calculated and used for prediction of new peptides that were then tested for antibacterial activity in order to improve peptide activity and to check the validity of the model. Models were also calculated including lactoferricins of different origin. Theories of the mechanism of action of the peptides are briefly discussed. Copyright © 2004 European Peptide Society and John Wiley&Sons, L

ISSN:1075-2617    

DOI:10.1002/psc.553

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractThe fully extended peptide conformation (2.05‐helix) has been investigated for the first time in the solid‐state by13C cross‐polarization magic angle spinning NMR. The compounds examined are members of a terminally protected, homo‐oligopeptide series (from monomer through hexamer) based on Cα, β‐didehydroalanine. Copyright © 2004 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.551

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractFasciculins are peptides isolated from mamba (Dendroaspis) venoms which exert their toxic action by inhibiting acetylcholinesterase (AChE). They contain a characteristic triple stranded antiparallel β‐sheet formed by residues 22–27, 34–39 and 48–53. A chimeric peptide named Fas‐C, encompassing most of these sequences was synthesized using SPPS/Boc‐chemistry and characterized chemically, structurally and functionally. Fas‐C has two disulfide bridges, formed sequentially using dual cysteine protection.SDS‐PAGE patterns, HPLC profiles and MS proved the peptide identity. Circular dichroism indicated the presence of 13.6% and 41.6% of β‐sheet and β‐turn, respectively, comparable to values observed in the native toxin. An inhibitory effect on eel AChE was displayed by the peptide (Ki71.6 ± 18.3 µM), although not reaching the affinity level of the parent native toxin (Ki0.3 nM). It is confirmed that the principal binding region of fasciculin to AChE resides within loop II. Copyright © 2004 European Peptide Society

ISSN:1075-2617    

DOI:10.1002/psc.554

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractFour monoepitopic MAPs (MAP A, B, C and E) and one bis‐diepitopic MAP B‐E derived from the primary sequence ofSchistosoma mansoniglyceraldehyde 3‐phosphate dehydrogenase, previously tested in BALB/c mice, were examined for their immunogenicity and protective capacity in C57BL/6 mice. Despite multimerization into MAPs, MAP A and MAP C were poorly immunogenic. In contrast to BALB/c mice, MAP E was non‐immunogenic in C57BL/6 mice. Peptide B in the form of MAP B or bis‐diepitopic MAP B‐E elicited immune responses in C57BL/6 mice that were associated with a significant decrease in worm burden.The MAPs were prepared by the stepwise solid‐phase peptide synthesis using Boc/Bzl chemistry, successfully purified on the RP‐HPLC column and characterized by RP‐HPLC, HPCE and MALDI‐TOF MS techniques. A general strategy for MAPs purification is discussed here and the purification of MAP B and MAP E is documented in detail. Copyright © 2004 European Peptide Society and

ISSN:1075-2617    

DOI:10.1002/psc.550

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractThe envelope proteins, gp120 and gp41 of HIV‐1, play a crucial role in receptor (CD4+lymphocytes) binding and membrane fusion. The fragment 254–274 of gp120 is conserved in all strains of HIV and, as a part of the full gp120 protein, behaves as ‘immunosilent’, but as an individual fragment it is ‘immunoreactive’. When this fragment binds to its receptor, it activates the fusion domain of gp41 allowing viral entry into the host CD4+cells. The conformation of fragment 254–274 of the gp120 domain and fragment 519–541 of the gp41 domain was studied by NMR and MD simulations. The studies were carried out in three varied media—water, DMSO‐d6and hexafluoroacetone (HFA). The fusogenic nature of the gp41 domain peptide was investigated by31P NMR experiments with model bilayers prepared from dimyristoyl‐L‐α‐phosphatidylcholine (DMPC). The solvent was seen to exert a major effect on the structure of the two peptides. Fragment (254–274) of gp120 in DMSO‐d6had a type I β‐turn around the tetrad Val9‐Ser10‐Thr11‐Gln12while in HFA a helical structure spanning the region Ile5to Gln12was seen with the remaining part of the peptide in a random coil structure. It is possible that the β‐turn may constitute an initiation site for the formation of the helix. In water at pH 4.5, the peptide adopted a β‐sheet. The NMR results for fragment 519–541 of gp41 are conclusive of a β‐sheet structure in DMSO‐d6, a conformation which may help in insertion into the membrane, a notion also put forward by others. The31P NMR studies of DMPC vesicles with this fragment show its fusogenic nature, promoting fusion of unilamellar vesicles to larger agglomerates like multilamellar ones. Copyright © 2

ISSN:1075-2617    

DOI:10.1002/psc.530

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractSilkmoth proteins secreted from the follicular cells that surround the oocyte form a large extracellular assembly which is important for protecting and sustaining the structure of the oocyte and the developing embryo. These proteins have been classified into two major families (A and B). Sequence analysis showed conservation of a central domain containing long stretches of six amino acid residue repeats in both families, which have been suggested to be organized in β‐sheet structures. In this work NMR and CD spectra, as well as molecular calculations, have been used to investigate the conformational properties of two synthetic peptides (A and B), analogues of parts of the central domain of silkmoth chorion proteins of the A and B families, respectively. These peptides consist of three tandem repeats of the six‐residue basic motif. Analysis of CD spectra of the two peptides in aqueous solutions and mixtures with organic solvents revealed β‐sheet and turn structural elements with a percentage higher than 40%. NOESY spectra at low temperatures (263–273 K) show sequential nOe connectivities (i, i+1), indicative of a relative flexibility. The presence of HNi‐HNi+1cross‐peaks and medium Hαi‐HNi+1connectivities, chemical shift deviations and temperature coefficient data provide, for the first time, experimental evidence that local folded structures around Gly residues occur in peptide segments of chorion proteins in solution. Simulated annealing calculations were used to examine the conformational space of the peptides and to probe the initial steps of amyloid fibril formation in the case of chorion proteins. Copyright © 2004 European Peptide Society and Joh

ISSN:1075-2617    

DOI:10.1002/psc.540

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY