摘要:

AbstractAn account is given of the life and work of G.G.F. Newton (1919–1969), joint discoverer with E.P. Abraham (1913–1999) of cephalosporin C. Copyright © 2008 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.1014

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY

摘要:

AbstractGlycopeptide dendrimers containing different types of tumor associated‐carbohydrate antigens (TN, TF, sialyl‐TN, sialyl‐TF, sialyl‐Lex, sialyl‐Leaetc.) were used in diagnosis and therapy of different sorts of cancer. These dendrimeric structures with incorporated T‐cell epitopes and adjuvants can be used as antitumor vaccines. Best results were obtained with multiantigenic vaccines, containing, e.g. five or six different TAAs. The topic of TAAs and their dendrimeric forms at molecular level are reviewed, including structure, syntheses, and biological activities. Use of glycopeptide dendrimers as antiviral vaccines against HIV and influenza is also described. Their syntheses, physico‐chemical properties, and biological activities are given with many examples. Copyright © 2008 European Peptide Society and John W

ISSN:1075-2617    

DOI:10.1002/psc.1011

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY

摘要:

AbstractA novel recombinant exendin‐4 human serum albumin fusion protein (rEx‐4/HSA) expressed inPichia pastoriswas prepared and characterized. Ex‐4 is a 39‐amino acid peptide isolated from the salivary gland of the lizardHeloderma suspectumand is thought to be a novel therapeutic agent for type 2 diabetes. But to gain a continued effect, the peptide has to be injected twice a day owing to its short plasma half‐life (t1/2= 2.4 h). To extend the half‐life of Ex‐4 moleculein vivo, we designed a genetically engineered Ex‐4/HSA fusion protein. Between Ex‐4 and HSA, a peptide linker GGGGS was inserted and the fusion protein was expressed in methylotrophic yeastP. pastoriswith native HSA secretion signal sequence. The recombinant protein was secreted correctly and was obtained with high purity (typically>98%) by a three‐step purification procedure. cAMP assay demonstrated that the fusion protein had a bioactivity similar to Ex‐4 for interaction with GLP‐1 receptorsin vitro. Results from oral glucose tolerance test indicated that rEx‐4/HSA could effectively improve glucose tolerance in diabetic db/db mice. Pharmacokinetics studies in cynomologus monkeys also showed that rEx‐4/HSA had a much longer plasma half‐life. Therefore, rEx‐4/HSA fusion protein could potentially be used as a new recombinant biodrug for type 2 diabetes therapy. Copyright © 2007 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.942

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY

摘要:

AbstractSolid‐phase synthesis and conformational studies of two pseudopeptides constituted by a triazine scaffold bound to two peptidic arms are described. In this paper, a new scaffold based on unsymmetrical triamino 1,3,5‐triazine bearing two alkyl chains has been designed, assisted by molecular modelling, as a mimic of the backbone of thei+ 1 andi+ 2 residues of a β‐turn. The results confirm the ability of the triazine scaffold to induce extended conformations of the peptidic strands and point out that this scaffold is a good candidate as a template to induce anti‐parallel β‐sheet structure. Copyright © 2007 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.944

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY

摘要:

AbstractIn the altered form of MUC1 mucin associated with breast cancer, the highly immunogenic sequence PDTRPAP is exposed, and may be an immunologically relevant target for the development of diagnostics or cancer immunotherapy. In this study, we report the preparation and antibody binding properties of monomeric and dimeric MUC1 peptides containing the epitope region recognized by monoclonal antibody (mAb) C595. Peptides contained a single or two copies of the whole 20‐mer repeat unit (VTSAPDTRPAPGSTAPPAHG) of MUC1 protein. MUC1 40‐mer peptides were prepared by the condensation of semi‐protected fragments of the repeat unit, in solution or by chemical ligation. In the first case, cyclohexyl‐type protecting groups were used for the synthesis of semi‐protected fragments by the Boc/Bzl strategy. Unprotected fragments were used in the chemical ligation to produce thioether linkages. In one of the fragments, a Gly residue was replaced by Cys at theC‐terminus and the other fragment was chloroacetylated at theN‐terminus. In addition, the short peptide APDTRPAPG, and its disulfide dimer, (APDTRPAPGC)2were produced. The antibody binding properties of these MUC1 peptide constructs were tested by competition enzyme‐linked immunosorbent assay (ELISA). The short epitope region peptide, APDTRPAPG and its dimer (APDTRPAPGC)2showed higherIC50values (IC50= 56.3 and 53.2 µmol/l, respectively). While the 20‐mer peptide (IC50= 25.9 µmol/l) and more markedly its 40‐mer dimers (IC50= 0.62 and 0.78 µmol/l) were recognized better. CD data obtained in water or in TFE indicated no significant conformational differences between the 20‐mer and 40‐mer peptides. We found a high level of similarity between the binding properties of the 40‐mer peptides with amide or thioether links, providing a new possibility to build up oligomeric MUC1 peptides by thioether bond formation. Copyright © 2007 European Peptide Soc

ISSN:1075-2617    

DOI:10.1002/psc.950

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY

摘要:

AbstractIn an attempt to identify regions in the leptin molecule responsible for its bioactivity, we tested six related‐leptin peptide fragments denoted: Ac‐hLEP23–47‐NH2(I), Ac‐hLEP48–71‐NH2(II), Ac‐hLEP72–88‐NH2(III), Ac‐hLEP92–115‐NH2(IV), Ac‐[Ser117]‐hLEP116–140‐NH2(V), Ac‐hLEP141–164‐NH2(VI) and their correspondent disulfide bridged dimer forms. The activity of the fragments was evaluated in comparision to leptin, by their ability to interact with leptin receptor using a cytosensor microphysiometer. Our results indicated that the fragmentsIVandVand [D‐Leu4]‐OB3and its human sequence analog were recognized by leptin receptor present in HP‐75 cells, in agreement with the results obtained by other workers, validating that this region of the molecule contain the functional epitope of the leptin molecule. Copyright © 2007 Eur

ISSN:1075-2617    

DOI:10.1002/psc.957

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY

摘要:

AbstractA bradykinin‐like peptide has been isolated from the skin secretions of the frogRana nigrovittata. This peptide was named ranakinin‐N. Its primary structure, RAEAVPPGFTPFR, was determined by Edman degradation and mass spectrometry. It is structurally related to bradykinin‐like peptides identified from skin secretions of other amphibians. Ranakinin‐N is composed of 13 amino acid residues and is related to the bradykinin identified from the skin secretions ofOdorrana schmackeri, which is composed of 9 amino acid residues. Ranakinin‐N was found to exert concentration‐dependent contractile effects on isolated guinea pig ileum. cDNA sequence encoding the precursor of ranakinin‐N was isolated from a skin cDNA library ofR. nigrovittata. The amino acid sequences deduced from the cDNA sequences match well with the results from Edman degradation. Analysis of different amphibian bradykinin cDNA structures revealed that the deficiency of a 15‐nucleotide fragment (agaatgatcagacgc in the cDNA encoding bradykinin fromO. schmackeri) in the peptide‐coding region resulted in the absence of a dibasic site for trypsin‐like proteinases and an unusual ‐AEVA‐ insertion in theN‐terminal part of ranakinin‐N. The ‐AEAV‐ insertion resulted in neutral net charge at theN‐terminus of ranakinin‐N. Ranakinin‐N is the first reported bradykinin‐like peptide with a neutral net charge at theN‐terminus. Copyright © 2007 Europea

ISSN:1075-2617    

DOI:10.1002/psc.958

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY

摘要:

AbstractA 24‐amino acid long peptide, Humanin, protects neurons from Alzheimer's disease (AD)‐related cell toxicities at sub‐nM‐uMconcentrations. Activity‐dependent neurotrophic factor (ADNF) is a glia‐derived neurotrophic peptide, which protects neurons from tetrodoxin treatment and AD‐related and amyotrophic lateral sclerosis‐related insults at fMconcentrations. An attempt was made to further improve the activity of Humanin by fusing this peptide to ADNF9, a 9‐amino acid long core peptide of the ADNF. This fusion resulted in a novel molecule, termed Colivelin, with the neuroprotective activity at fMrange, which is ∼103–107fold higher than the activity of Humanin and Humanin analogs and follows the activity profile of fM‐active ADNF9. We have characterized the structural properties of Colivelin and compared with those of ADNF9 and Humanin in water and phosphate‐buffered saline (PBS). The secondary structure of Colivelin was similar to that of ADNF9, but not that of Humanin, and hence was not the average of the contributions of the two peptides fused. Colivelin was stable and monomeric in PBS, consistent with the monomeric property of ADNF9, while Humanin showed strong tendency to self‐associate. Thus, it is evident that the structural properties of Colivelin resemble those of ADNF9, rather than those of Humanin. Copyright © 2007 European Peptide Soci

ISSN:1075-2617    

DOI:10.1002/psc.959

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY

摘要:

AbstractMammalian thioredoxin reductase (TR) catalyzes the reduction of the redox‐active disulfide bond of thioredoxin (Trx) and is similar in structure and mechanism to glutathione reductase except for aC‐terminal 16‐amino acid extension containing a rare vicinal selenylsulfide bond. This vicinal selenylsulfide bond is essentially a substrate for the enzyme'sN‐terminal redox center. Here we report the synthesis of peptide substrates for the truncated enzyme missing theC‐terminal redox center. We developed a procedure for the synthesis of peptides containing cyclic vicinal disulfide/selenylsulfide bonds as well as their corresponding acyclic heterodimers. Vicinal disulfide bonds form eight‐membered ring structures and are difficult to synthesize owing to their propensity to dimerize during oxidation. Our procedure makes use of two key improvements for on‐resin disulfide bond formation presented previously by Galande and coworkers (Galande AK, Weissleder R, Tung C‐H. An effective method of on‐resin disulfide bond formation in peptides.J. Comb. Chem.2005;7: 174–177). First, the addition of an amine base to the deprotection solution allows the complete removal of the StBu group, allowing it to be replaced with a 5‐Npys group. The second enhancement is the direct use of a Cys(Mob) or Sec(Mob) derivative as the nucleophilic partner instead of utilizing a naked sulfhydryl or selenol. These improvements result in the formation of a vicinal disulfide (or selenylsulfide) bond in high purity and yield. A direct comparison with the Galande procedure is presented. We also present a novel strategy for the formation of an acyclic, interchain selenylsulfide‐linked peptide (linking H‐PTVTGC‐OH and H‐UG‐OH). Cysteine analogs of the cyclic and acyclic peptides were also synthesized. The results show that the ring structure contributes a factor of 52 to the rate, but the presence of selenium in the peptide is more important to catalysis than the presence of the ring. Copyright © 2007 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.961

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY

摘要:

AbstractThe crystal structures of two oligopeptides containing di‐n‐propylglycine (Dpg) residues, Boc‐Gly‐Dpg‐Gly‐Leu‐OMe (1) and Boc‐Val‐Ala‐Leu‐Dpg‐Val‐Ala‐Leu‐Val‐Ala‐Leu‐Dpg‐Val‐Ala‐Leu‐OMe (2) are presented. Peptide1adopts a type I′β‐turn conformation with Dpg(2)–Gly(3) at the corner positions. The 14‐residue peptide2crystallizes with two molecules in the asymmetric unit, both of which adopt α‐helical conformations stabilized by 11 successive 5 → 1 hydrogen bonds. In addition, a single 4 → 1 hydrogen bond is also observed at theN‐terminus. All five Dpg residues adopt backbone torsion angles (ϕ, ψ) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle NCαC′(τ) and the observed backbone ϕ,ψ values. For τ>106° , helices are observed, while fully extended structures are characterized by τ<106° . The mean τ values for extended and folded conformations for the Dpg residue are 103.6° ± 1.7° and 109.9° ± 2.6

ISSN:1075-2617    

DOI:10.1002/psc.962

出版商:John Wiley&Sons, Ltd.    

年代:2008

数据来源: WILEY