ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200005)6:5<201::AID-PSC250>3.0.CO;2-H

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractTwo methionine‐containing peptides, endothelin 1 and the 1–16 fragment of the receptor of the plasminogen activator 1 for human urokinase, were synthesized and cyclized by hydrogen peroxide. Endothelin 1 was obtained by using regioselective and random schemes of disulfide bond formation. The conditions of cyclization that provided the target products in high purity were found. The general potential of disulfide bond formation by means of hydrogen peroxide was demonstrated for methionine‐containing peptides. The method resulted in target products containing insignificant quantities of the corresponding Met‐sulfoxide derivatives. Copyright © 2000 European Peptide Society and John Wiley&S

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200005)6:5<208::AID-PSC241>3.0.CO;2-V

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractThe multiple antigenic peptide system (MAP) has been proposed as a novel and valuable approach for eliciting antibodies for peptides and developing synthetic vaccines. Multi‐epitope polypeptides (MEP) have also been developed as an alternative to the recombinant approach for vaccines. The V3 loop from the HIV type 1 (HIV‐1) external glycoprotein (gp120) contains the principal neutralization domain (PND). Antibodies against this region neutralize HIV‐1in vitroandin vivo. In this work, a novel presentation of di‐epitope MAP was synthesized. A monomeric MAP carrying two identical JY1 V3 sequences as B‐cell epitopes and the 830–843 region of tetanus toxoid as a T‐helper cell epitope was synthesized. This basic structure was covalently linked to produce a four‐JY1‐branched homodimer (JY1‐MAP4). Additionally, six different monomeric MAPs, bearing four copies of V3 from isolates LR150, JY1, RF, MN, BRVA and IIIB, were synthesized. These monomers were conveniently linked among themselves to produce homodimeric and heterodimeric MAPs of eight V3 branches (V3‐MAP8). JY1‐MAP8 elicited higher antibody titers in Balb/c mice than JY1‐MAP4. The immunogenicity of two different, hexavalent V3‐MAP8 mixtures and the MEP TAB9, which tandems the same six V3 sequences in a single molecule, were compared. The antibody response against the mixtures of the heterodimeric MAP showed a wider recognition pattern of the V3 region, while the homodimeric cocktail showed an intermediate pattern. Antibodies elicited by TAB9 recognized only the JY1, LR150 peptides. These results emphasize the influence of V3 epitope presentation upon the characteristics of the antibody response generated. Copyright © 2000 European Peptide Soci

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200005)6:5<217::AID-PSC242>3.0.CO;2-U

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractEstablished methodology for the preparation of peptide thioesters requires the use oft‐butoxycarbonyl chemistry owing to the lability of thioester linkers to the nucleophilic reagents used in Fmoc solid phase peptide synthesis. Both the greater ease of use and the broad applicability of the method has led to the development of an Fmoc‐based methodology for direct peptide thioester synthesis. It was found that successful preparation of a peptide thioester could be achieved when the non‐nucleophilic base, 1,8‐diazabicyclo[5.4.0]undec‐7‐ene, together with 1‐hydroxybenzotriazole in dimethylformamide, were used as theNα‐Fmoc deprotection reagent. Native chemical ligation of the resulting thioester product to anN‐terminal cysteine‐containing peptide was successfully performed in aqueous solution to produce a fragment peptide of human α‐synuclein. The formation of aspartimide (cyclic imide) in a base‐sensitive hexapeptide fragment of scorpion toxin II was found to be significant under the deprotection conditions used. However, this could be controlled by the judicious protection of sensitive residues using the 2‐hydroxy‐4‐methoxybenzyl group. Copyright © 2000 European Peptide

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200005)6:5<225::AID-PSC244>3.0.CO;2-T

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractThe ‘template‐assembled synthetic protein’ (TASP) concept provides a simple and elegant approach for the preparation of analogues that retain key structural elements. We have synthesized TASP molecules containing the putative active site of relaxin, a peptide that has similar structural features to insulin but a markedly different biological role. Two types of chemoselective thiol ligation strategies (thioether and thiazolidine) were used and compared. The synthetic pendant peptides contain an essential region for bioactivity that is located in the α‐helical region of the relaxin B‐chain. Depending on whether the thioether or the thiazolidine chemistry was used to attach the peptides to the template, the reacting amino acid was placed either at theC‐terminus orN‐terminus, respectively, thus allowing the choice of orientation relative to the carrier molecule. The template molecule consists of a decapeptide with two proline–glycine turns and four evenly spaced lysine residues that were functionalized with the appropriate chemical moiety. This allowed reaction with the appropriately derivatized peptides in solution. To improve the template ligation step using the thioether approach, a pendant peptideC‐terminal cysteamine residue was used to reduce potential steric hindrance during conjugation. The design of the peptides as well as the synthetic strategy resulted in the acquisition of mimetics showing weak non‐competitive and weak competitive antagonist properties. Copyright © 2000 European Peptide Society and

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200005)6:5<235::AID-PSC247>3.0.CO;2-J

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractA new aminoethyl‐polystyrene linker, stable at low concentrations of TFA, has been developed for the solid phase synthesis of peptide amides. The described linker is stable under conditions which remove Butprotecting groups (30–50% TFA in DCM) and the desired product can be finally cleaved off the solid support in 95% TFA (5% H2O). Model peptide amides and otherN‐alkylated peptide amides have been successfully synthesized in good yield and purity. Copyright © 2000 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200005)6:5<243::AID-PSC251>3.0.CO;2-4

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY