摘要:

AbstractThe aromatic amino acids Tyr and Phe in angiotensin IV (Ang IV) were conformationally constrained by the use of β‐Me substituted analogs, or cyclic constrained analogs. None of these modifications was allowed for Tyr1, while onlye‐β‐MePhe6substitution resulted in an AngIV analog with high IRAP potency and selectivityversusAP‐N or the AT1receptor. This indicates an important role of the orientation of the Phe6for inducing selectivity. Pro5replacement with 2‐aminocyclopentanecarboxylic acid maintained IRAP potency and abolished AT1affinity. These results confirm the importance of conformational constrained amino acids to generate selectivity in bioactive peptides. Copyright © 2011 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.1365

出版商:John Wiley&Sons, Ltd.    

年代:2011

数据来源: WILEY

摘要:

AbstractIn this study, ten tetra‐ and heptapeptide analogues of deltorphin containing the urea bridges between residues 2 and 4 have been docked into the δ‐ and µ‐opioid receptors to explain their different biological activities. The important factors explaining particular ligand activity such as free energy of binding, conformation of the ligand, its location inside the binding pocket as well as the number and strength of the receptor–ligand interactions have been discussed. Several different binding modes for investigated ligands have been proposed. It appears that the binding site is not identical even for very similar ligands. Results of this study help to explain the differences in biological activity of the deltorphin analogues, their interaction with the opioid receptors at the molecular level and support designing a new generation of potent opioid drugs with improved selectivity. Copyright © 2011 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.1371

出版商:John Wiley&Sons, Ltd.    

年代:2011

数据来源: WILEY

摘要:

AbstractA 7‐mer peptide (S‐T‐L‐P‐L‐P‐P) that bound to various divalent cations was selected from a phage display peptide library. Isothermal calorimetric analysis revealed that the peptide bound to Pb2+, Cd2+, Hg2+, and Cu2+. Through the use of CD studies, no secondary structural changes were observed for the peptide upon binding to divalent cations. Ala scanning mutant peptides bound to Hg2+with a reduced affinity. However, no single substitution was shown to affect the overall affinity. We suggest that Pro residues chelate divalent cations, while the structure formed by the peptide is also important for the binding process. Copyright © 2011 European Peptide Society and John W

ISSN:1075-2617    

DOI:10.1002/psc.1374

出版商:John Wiley&Sons, Ltd.    

年代:2011

数据来源: WILEY

摘要:

AbstractHTLV‐I is a debilitating and/or lethal retrovirus that causes HTLV‐I‐associated myelopathy/tropical spastic paraparesis, adult T‐cell leukemia and several inflammatory diseases. HTLV‐I protease is an aspartic retropepsin involved in HTLV‐I replication and its inhibition could treatHTLV‐I infection. A recombinant L40I mutant HTLV‐I protease was designed and obtained fromEscherichia coli, self‐processingand purification by ion‐exchange chromatography. The protease was refolded by a one‐step dialysis and recovered activity. The cleavage efficiency of the [Ile40]HTLV‐I protease was at least 300 times higher for a fluorescent substratethan that of our previously reported recombinant His‐tagged non‐mutated HTLV‐I protease. In addition, we designed and synthesized a substrate containing a highly fluorescent Mca moiety in the fragment before the scissile bond, and a chromogenicp‐nitrophenylalanine moiety after the scissile bond that greatly amplified spectrometry detection and improved the HTLV‐I protease inhibition potency assay. The HTLV‐I protease inhibition assay with the [Ile40]HTLV‐I protease and fluorogenic substrate requires distinctively less protease, substrate, inhibitor and assay time than our previous methods. This means our new assay is more cost‐effective and more time‐efficient while being reproducible and less labor‐intensive. Copyright © 2011 Europ

ISSN:1075-2617    

DOI:10.1002/psc.1375

出版商:John Wiley&Sons, Ltd.    

年代:2011

数据来源: WILEY

摘要:

AbstractAn improved synthesis of (2S, 4S)‐ and (2S, 4R)‐2‐amino‐4‐methyldecanoic acids was accomplished using a glutamate derivative as starting material and Evans' asymmetric alkylation as the decisive step. The NMR data of the two diastereomers were measured and compared with those of the natural product. As a result, the stereochemistry of this novel amino acid unit in culicinins was assigned as (2S, 4R). Copyright © 2011 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.1376

出版商:John Wiley&Sons, Ltd.    

年代:2011

数据来源: WILEY

摘要:

AbstractThe labyrinthopeptins are a new class of lantibiotics containing two identical quaternary α,α‐disubstituted amino acids, named labionin (Lab). The synthetic formation of this unique structural feature represents the key step in the total synthesis of these polycyclic peptides. In this report we describe the synthesis of an orthogonally protected α,α‐disubstituted amino acid building block serving as labionin precursor for the future assembly of labyrinthopeptin A2 and of other labyrinthopeptin derivatives. Copyright © 2011 European Peptide Society and John Wiley&S

ISSN:1075-2617    

DOI:10.1002/psc.1378

出版商:John Wiley&Sons, Ltd.    

年代:2011

数据来源: WILEY

摘要:

AbstractThe medium‐length peptaibiotics are characterized by a primary structure of 14–16 amino acid residues. Despite the interesting antibiotic and antifungal properties exhibited by these membrane‐active peptides, their exact mechanism of action is still unknown. Here, we present our results on heptaibin, a 14‐amino acid peptaibiotic found to exhibit antimicrobial activity againstStaphylococcus aureus. We carried out the very challenging synthesis of heptaibin on solid phase and a detailed conformational analysis in solution. The peptaibiotic is folded in a mixed 310‐/α‐helix conformation which exhibits a remarkable amphiphilic character. We also find that it is highly stable toward degradation by proteolytic enzymes and nonhemolytic. Finally, fluorescence leakage experiments using small unilamellar vesicles of three different compositions revealed that heptaibin, although uncharged, is a selective compound for permeabilization of model membranes mimicking the overall negatively charged surface of Gram‐positive bacteria. This latter finding is in agreement with the originally published antimicrobial activity data. Copyright © 2011 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.1364

出版商:John Wiley&Sons, Ltd.    

年代:2011

数据来源: WILEY

摘要:

AbstractP14C/N39C is the disulfide variant of the ovomucoid third domain from silver pheasant (OMSVP3) introducing an engineered Cys14Cys39bond near the reactive site on the basis of the sequence homology between OMSVP3 and ascidian trypsin inhibitor. This variant exhibits a narrower inhibitory specificity. We have examined the effects of introducing a Cys14Cys39bond into the flexible N‐terminal loop of OMSVP3 on the thermodynamics of the reactive site peptide bond hydrolysis, as well as the thermal stability of reactive site intact inhibitors. P14C/N39C can be selectively cleaved byStreptomyces griseusprotease B at the reactive site of OMSVP3 to form a reactive site modified inhibitor. The conversion rate of intact to modified P14C/N39C is much faster than that for wild type under any pH condition. The pH‐independent hydrolysis constant (Khyd°) is estimated to be approximately 5.5 for P14C/N39C, which is higher than the value of 1.6 for natural OMSVP3. The reactive site modified form of P14C/N39C is thermodynamically more stable than the intact one. Thermal denaturation experiments using intact inhibitors show that the temperature at the midpoint of unfolding at pH 2.0 is 59 °C for P14C/N39C and 58 °C for wild type. There have been no examples, except P14C/N39C, where introducing an engineered disulfide causes a significant increase inKhyd°, but has no effect on the thermal stability. The site‐specific disulfide introduction into the flexible N‐terminal loop of natural Kazal‐type inhibitors would be useful to further characterize the thermodynamics of the reactive site peptide bond hydrolysis. Copyright © 2011 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.1381

出版商:John Wiley&Sons, Ltd.    

年代:2011

数据来源: WILEY