ISSN:1075-2617    

DOI:10.1002/psc.1123

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractSince the discovery of the proteasome and its structure elucidation intensive research programs in academic institutions and pharmaceutical industries led to identification of a wide spectrum of synthetic and natural small proteasomal inhibitors. Activity studies with these small molecules helped to deeply understand the complex biochemical organization and functioning of the proteasome. The new structural and biochemical insights placed the proteasome as an important anti‐cancer drug target, as revealed by the dipeptide boronate proteasome inhibitor, bortezomib, which is currently used for treatment of multiple myeloma. Serious side effects and partial cell resistance against bortezomib demand creation and discovery of new improved generations of more specific and potent proteasomal inhibitors. Copyright © 2008 European Peptide Society and John Wiley&Sons, L

ISSN:1075-2617    

DOI:10.1002/psc.1107

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractGrowing interest in synthetic peptides carrying post‐traslational modifications, in general, and the Amadori modification in particular, raises the need for specific building blocks that can be used in stepwise peptide synthesis. Herein, we report the synthesis ofNα‐Fmoc‐Lys‐OH derivatives containingNε‐1‐deoxyfructopyranosyl moiety. Copyright © 2008 European Peptide Society and John W

ISSN:1075-2617    

DOI:10.1002/psc.1105

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractWe report the first example of conopeptide oxidation performed in a biocompatible ionic liquid, 1‐ethyl‐3‐methylimidazolium acetate ([C2mim][OAc]), which enables the efficient formation of both hydrophilic and poorly water‐soluble conotoxins compared with conventional methods. Moreover, the method features a high‐concentration approach ultimately leading to higher yields at reduced separation effort. Copyright © 2008 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.1106

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractThe membrane‐bound rat GH‐R and an alternatively spliced isoform, the soluble rat GH‐BP, are comprised of identicalN‐terminal GH‐binding domains; however, theirC‐terminal sequences differ. Immunological reagents are needed to distinguish between the two isoforms in order to understand their respective roles in mediating the actions of GH. Accordingly, a tetravalent MAP dendrimer with four identical branches of aC‐terminal peptide sequence of the rat GH‐BP (GH‐BP263–279) was synthesized and used as an immunogen in rabbits. Solid‐phase peptide synthesis of four GH‐BP263–279segments onto a tetravalent Lys2‐Lys‐β‐Ala‐OH core peptide was carried out using Fmoc chemistry. The mass of the RP‐HPLC‐purified synthetic product, 8398 Da, determined by ESI‐MS, was identical to expected mass. Three anti‐rat GH‐BP263–279MAP antisera, BETO‐8039, BETO‐8040, and BETO‐8041, at dilutions of 10−3, recognized both the rat GH‐BP263–279MAP and recombinant mouse GH‐BP with ED50s within a range of 5–10 fmol, but did not cross‐react with BSA in dot blot analyses. BETO‐8041 antisera (10−3dilution) recognized GH‐BPs of rat serum and liver having Mrs ranging from 35 to 130 kDa, but did not recognize full‐length rat GH‐Rs. The antisera also detected recombinant mouse GH‐BPs. In summary, the tetravalent rat GH‐BP263–279MAP dendrimer served as an effective immunogenic antigen in eliciting high titer antisera specific for theC‐termini of both rat and mouse GH‐BPs. The antisera will facilitate studies aimed at improving our understanding of the b

ISSN:1075-2617    

DOI:10.1002/psc.1096

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractSize exclusion chromatographic analyses showed that Ca2+‐free VILIP‐1 contained both monomeric and dimeric forms, while no appreciable dimerization was noted with Ca2+‐free VILIP‐3. Swapping of EF‐hands 3 and 4 of VILIP‐1 with those of VILIP‐3 caused the inability of the resulting chimeric protein to form dimeric protein. Nonreducing SDS‐PAGE analyses revealed that most of the dimeric VILIP‐1 was noncovalently bound together. Reduced glutathione (GSH)/oxidized glutathione (GSSG) treatment notably enhanced the formation of disulfide‐linked VILIP‐1 dimer, while Ca2+and Mg2+enhanced disulfide dimerization of VILIP‐1 marginally in the presence of thiol compounds. Cys‐187 at the C‐terminus of VILIP‐1 contributed greatly to form S‐S‐crosslinked dimer as revealed by mutagenesis studies. The ability of GSH/GSSG‐treated VILIP‐1 to activate guanylyl cyclase B was reduced by substituting Cys‐187 with Ala. Together with disulfide dimer of VILIP‐1 detected in rat brain extracts, our data may imply the functional contribution of disulfide dimer to the interaction of VILIP‐1 with its physiological target(s). Copyright © 2008 Europ

ISSN:1075-2617    

DOI:10.1002/psc.1097

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to examine the effects of structural parameters of peptides on their oxidation by DMSO, including location of cysteine, effect of adjunct group participation, molecular hydrophobicity, steric hindrance or the accessibility of thiol group and peptide conformation, on oxidation rates, dimer formation and associated side products. We designed and synthesized two series of linear cysteine‐containing analogues of human β‐defensin 3 (the C1‐peptides with cysteine at theN‐terminus residue 1, the C29‐peptides with cysteine located at residue 29 in the centre of peptide), which were used for preparation of disulphide‐linked homodimers. HPLC–ESI–MS was used to monitor the oxidation process and to characterize the molecular weights of dimers and side products of high oxidation. The formations of dimers and side products were dependent on the position of cysteines. Hydrophobicity generally rendered the thiol groups less accessible and hence exposed them to slow oxidation to form dimers (or even fail to form dimers during the timescale of observation). Molecular dynamics simulations showed that the exposure of cysteines (and sulphurs) of the C1‐peptides was much larger than for the C29‐peptides. The larger hydrophobic side chains tended to enable clustering of the side chains that sequester cysteine, particularly in the C29‐peptides, which provided a molecular explanation for the observed trends in oxidation rates. Together with molecular modelling, we propose a reaction mechanism to elucidate the oxidation results of these peptides. Copyright © 2008 European Peptide Society a

ISSN:1075-2617    

DOI:10.1002/psc.1100

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractA series of peptidomimetics intended to promote the β‐hairpin motif have been studied. Structural variations include a turn region with and without a photoswitchable chromophore, and strands with amino acid side chains supporting various degrees of interstrand interactions for hairpin stabilisation. The propensity of the compounds to form β‐hairpins was evaluated experimentally by NMR spectroscopy, translational self‐diffusion studies and CD spectroscopy. In the presence of hairpin stabilising interstrand interactions, the structurally flexible stilbene chromophore appeared to be well compatible with the imposed secondary structure. Copyright © 2008 European Peptide Society and John Wiley&S

ISSN:1075-2617    

DOI:10.1002/psc.1103

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY

摘要:

AbstractA cationic peptide, Td3701, which was derived from factor VIII that has affinity with phosphatidylserine (PS), showed efficient transfection ability for cells that express PS on the cell surface. PS is exposed on tumor cell surfaces therefore we have focused on PS as the target molecule for tumor specific gene delivery. In this article, to improve transfection efficiency and specificity in targeting tumor cells, some amino acid residues of Td3701 were replaced. The resulting peptide, Td3717, shows higher transfection efficiency (more than 30 times that of Td3701). The transfection efficiency was dependent on the amount of PS on the cell surface, suggesting that Td3717 bound with plasmid DNA could recognize PS on the cell surface. Td3717 is expected to be useful as an efficient gene carrier molecule specific to PS‐presenting tumor cells. Copyright © 2008 European Peptide Society and John Wiley&Sons, L

ISSN:1075-2617    

DOI:10.1002/psc.1104

出版商:John Wiley&Sons, Ltd.    

年代:2009

数据来源: WILEY