摘要:

AbstractThe synthesis of peptide bonds catalysed by subtilisinCarlsbergwas studied in different hydrophilic organic solvents with variable H2O concentration. Z‐Val‐Trp‐OMe and Z‐Ala‐Phe‐OMe were used as acyl donors, and a series of amino acid derivatives, di‐ and tripeptides of the general structure Xaa‐Gly, Gly‐Xaa, Gly‐Gly‐Xaa (Xaa represents all natural L‐amino acids except cysteine) and other peptides were used as nucleophiles. A comparative study of the enzymatic synthesis in aqueous DMF (50%, v/v) and acetonitrile containing 10% (v/v) of H2O demonstrated that the yields of peptide products were higher in most cases when acetonitrile with low H2O concentration was used. The acylation of weak nucleophiles was improved in organic solvents with very low H2O concentration (2%). The reactions in anhydrous But‐OH proceeded with substantially lower velocity. Generally, the restricted nucleophile specificity of the enzyme for glycine and hydrophilic amino acid residues in P1′ position, as well as numerous side reactions, limit the utilization of subtilisin in peptide synthesis, especially in the case of the segment condensations. Contrary to the published data, we have proved that proline derivatives were not acylated in any media with the help of subtilisin Carlsberg. Effective ester hydrolysis of a protected nonapeptide corresponding to the N‐terminal sequence of dicarba‐eel‐calcitonin catalysed by sublilisin was achieved. Copyright © 2000 European Peptid

ISSN:1075-2617    

DOI:10.1002/1099-1387(200011)6:11<541::AID-PSC271>3.0.CO;2-T

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractPathological changes in the microtubule associated protein tau, leading to tau‐containing filamentous lesions, are a major hallmark common to many types of human neurodegenerative diseases, including Alzheimer's disease (AD). No structural data are available which could rationalize the extensive conformational changes that occur when tau protein is converted to Alzheimer's paired helical filaments (PHF). The C‐terminal portion of tau plays a crucial role in the aggregation of tau into PHF and in the truncation process that generates cytotoxic segments of tau. Therefore, we investigated the solution structure of the hydrophobic C‐terminal segment 423–441 of tau protein (PQLATLADEVSASLAKQGL) by1H 2D NMR spectroscopy. The peptide displays the typical NMR evidence consistent with a α‐helix geometry with a stabilizing C‐capping motif. The reported data represent the first piece of structural information on an important portion of the molecule and can have implications towards the understanding of its pathophysiology. Copyright © 2000 European Peptide Society and John Wi

ISSN:1075-2617    

DOI:10.1002/1099-1387(200011)6:11<550::AID-PSC272>3.0.CO;2-S

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractIn this paper, we report the difficult synthesis of cyclo(Leu‐Pro‐Leu‐Pro). While the cyclization of Leu‐Pro‐Leu‐D‐Pro did not cause problems, the all‐L‐peptide afforded cyclodimer rather than cyclotetrapeptide (cyclomonomer). A first attempt using our reversible backbone substitution methodology failed. However, we were successful in obtaining the desired cyclo(Leu‐Pro‐Leu‐Pro) by decreasing the concentration. The ratio of cyclomonomer to cyclodimer was raised to 1:1.1 using BOP and 1:0.6 using HATU under our high dilution condition. The structures of the cyclopeptides were confidently assigned by electrospray ionization mass spectrometry and NMR. Copyright © 2000 European Peptide Society

ISSN:1075-2617    

DOI:10.1002/1099-1387(200011)6:11<560::AID-PSC275>3.0.CO;2-I

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractTwo complete series of N‐protected oligopeptide esters to the pentamer level from 1‐amino‐cycloundecane‐1‐carboxylic acid (Ac11c), an α‐amino acid conformationally constrained through a medium‐ring Cαi↔Cαicyclization, and either theL‐Ala or Aib residue, along with the N‐protected Ac11c monomer and homo‐dimer alkylamides, have been synthesized by solution methods and fully characterized. The preferred conformation of these model peptides has been assessed in deuterochloroform solution by FT‐IR absorption and1H‐NMR techniques. Furthermore, the molecular structures of one derivative (Z‐Ac11c‐OH) and two peptides (the tripeptide ester Z‐Aib‐Ac11c‐Aib‐OtBu and the pentapeptide ester Z‐Ac11c‐(Aib)2‐Ac11c‐Aib‐OtBu) have been determined in the crystal state by X‐ray diffraction. The experimental results support the view that β‐bends and 310‐helices are preferentially adopted by peptides rich in Ac11c, the second largest cycloaliphatic Cα,α‐disubstituted glycine known. This investigation has allowed the authors to approach the completion of a detailed conformational analysis of the whole 1‐amino‐cycloalkane‐1‐carboxylic acid (Acnc, with n=3–12) series, which represents the prerequisite for their recent proposal of the ‘Acnc scan’

ISSN:1075-2617    

DOI:10.1002/1099-1387(200011)6:11<571::AID-PSC290>3.0.CO;2-R

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY