摘要:

AbstractThe abbreviations and symbols used in Peptide Science are surveyed, with comment and recommendations. Copyright © 2005 European Peptide Society and John Wiley&Sons, Ltd

ISSN:1075-2617    

DOI:10.1002/psc.725

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractThe solution conformation of vasopressin analogues, modified at positions 2 and 3 withN‐methylphenylalanine or its enantiomer, [D‐MePhe2,MePhe3]AVP and [MePhe2,D‐MePhe3]AVP, were studied by 2D NMR spectroscopy in H2O/D2O and theoretical calculations (EDMC/ANALYZE). In the case of [MePhe2,D‐MePhe3]AVP, the synthesis afforded two products,AandB, which had identical molecular ions and similar retention times on HPLC. This finding was explained by racemization of Cys1, which gave an additional analogue, [D‐Cys1,MePhe2,D‐MePhe3]AVP (B). The possibility is not excluded of racemization of Cys1in the remaining analogues of this series. However, only in the case of [MePhe2,D‐MePhe3]AVP was this process so distinct that two strong peaks in the HPLC chromatogram were observed. The NMR spectra of all the analogues showed several distinct sets of residual proton resonances. This suggests that the peptides adopt more than two groups of conformations in H2O/D2O. This fact is due tocis/transisomerization. Two more populated isomers arise from thecis/transisomerization across the 2–3 peptide bond in [D‐MePhe2,MePhe3]AVP and [MePhe2,D‐MePhe3]AVP (A) and across the 1–2 peptide bond in [D‐Cys1,MePhe2,D‐MePhe3]AVP (B). Copyright © 2005 European Peptide Societ

ISSN:1075-2617    

DOI:10.1002/psc.684

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractNovel analogs of human monocyte chemoattractant protein 1 (MCP‐1) were designed, synthesized and characterized to be used as tools to generate monoclonal antibodies as potential human therapeutics. MCP‐1 and three analogs were synthesized by step‐wise Fmoc solid phase synthesis. After oxidation to form the two‐disulfide bonds, affinity chromatography using an immobilized mouse anti‐human MCP‐1 monoclonal antibody (mAb) was utilized for a simple and highly effective purification procedure for the proteins. The final products were extensively characterized and compared with recombinant human MCP‐1 (rhMCP‐1). All proteins showed identical binding with mouse anti‐human MCP‐1 mAbs as measured by surface plasmon resonance. Synthetic MCP‐1 and the analogs were comparable to recombinant MCP‐1 in competition radio‐ligand binding to CCR2 receptors on THP‐1 cells, and MCP‐1‐induced, calcium mobilization and chemotaxis assays. Copyright © 2005 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.680

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractIn this paper, a simulation of the folding process, based on a random perturbations of the ϕ, ψ, χ1dihedral angles, is proposed to approach the formation at the atom level of both principal elements of protein secondary structure, the α‐helix and the β‐hairpin structures. Expecting to understand what may happen in solution during the formation of such structures, the behaviour of large sets of random conformations that are generated for small oligopeptides was analysed. Different factors that may influence the folding (as conformational propensity, hydrophobic interactions and side‐chain mobility) were investigated. The difference between the corresponding theoretical folding and the real conformational diversity that is observed in solution is appraised by a comparison between the calculated and observed NMR secondary chemical shifts. From this study it appears that hydrophobic interactions and mobility represent the principal factors that initiate folding and determine the observed hydrogen‐bond pattern, which subsequently allows packing between the peptide side chains. Copyright © 2005 European Peptide Society and John Wi

ISSN:1075-2617    

DOI:10.1002/psc.694

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractA novel liposomal formulation was developed for the encapsulation of the oligopeptide leuprolide (GlpHisTrpSerTyr‐D‐LeuLeuArgProNHEt), a potent analogue of gonadotropin releasing hormone used in the treatment of advanced prostate cancer, endometriosis and precocious puberty. Leuprolide was synthesized using solid phase methodology on a {3‐[(ethyl‐Fmoc‐amino)‐methyl]‐1‐indol‐1‐yl}‐acetyl AM resin and Fmoc/tBu chemistry. The new liposomal formulation, called ‘liposomes in liposomes’ is composed of egg phosphatidylcholine:dipalmitoylphosphatidylglycerol in a molar ratio of 98.91:1.09 (internal liposomes) and egg phosphatidylcholine:dipalmitoylphosphatidylglycerol:cholesterol in a molar ratio of 68.71:0.76:30.53 (external liposomes). It offers high encapsulation efficiency (73.8% for leuprolide); it can provide new delivery characteristics and it may have possible advantages in future applications regarding the encapsulation and delivery of bioactive peptides to target tissues. Furthermore, the physicochemical characteristics (size distribution and ζ‐potential) of the liposomal formulations and the thermal effects on leuprolide in model lipidic bilayers composed of dipalmitoylphosphatidylcholine were studied using differential scanning calorimetry. Finally, the dynamic effects of leuprolide in an egg phosphatidylcholine/cholesterol system were examined using solid state13C MAS NMR spectroscopy. Copyright © 2005 European Peptide Soc

ISSN:1075-2617    

DOI:10.1002/psc.681

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractThe solution conformation of human calcitonin in a mixture of 60% water and 40% trifluoroethanol has been determined by the combined use of1H NMR spectroscopy and distance geometry calculations with a distributed computing technique.1H NMR spectroscopy provided 195 distance constraints and 13 hydrogen bond constraints. The 20 best converged structures exhibit atomic rmsd of 0.43 Å for the backbone atoms from the averaged coordinate position in the region of Asn3—Phe22. The conformation is characterized by a nearly amphiphilic α‐helix domain that extends from Leu4in the cyclic region to His20. There are no significant differences observed among the overall structures of a series of calcitonins obtained from ultimobranchial bodies, including those that possess 20‐ to 50‐fold greater activity. Three aromatic amino acid residues, Tyr12, Phe16and Phe19, form a hydrophobic surface of human calcitonin. Bulky side chains on the surface could interfere with the ligand–receptor interaction thereby causing its low activity, relative to those of other species. Copyright © 2005 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.687

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractSolid phase synthesis of BH4, the 26 amino‐acid domain (6RTGYDNREIVMKYIHYKLSQRGYEWD31) of the anti‐apoptotic Bcl‐2 protein has been accomplished using Fmoc chemistry. The use of peculiar cleavage conditions provided high yields after purification such that tens to hundreds of mg could be obtained. A15N‐labelled version of the peptide could also be synthesized for NMR studies in membranes. The peptide purity was not lower than 98% as controlled by UV and MALDI‐TOF mass spectrometry. The secondary structure was determined in water, trifluoroethanol (TFE) and in lipid membrane using UV circular dichroism. The peptide shows dominant β‐sheeted structures in water that convert progressively into α‐helical features upon addition of TFE or membrane. The amphipathic character of the helix suggests that the peptide might have a structure akin to those of antimicrobial peptides upon interaction with membranes. Copyright © 2005 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.686

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractOligopeptidase B is a serine endopeptidase found in prokaryotes, unicellular eukaryotes and higher plants. The enzyme has been shown recently to play a central role in the pathogenesis of several parasitic diseases such as African trypanosomiasis, and to be a potential therapeutic target. This study reports that protamine, a basic peptide rich in arginine, is a potent inhibitor at the nanomolar level of oligopeptidase B fromE. coliand wheat. Protamines 1B, 2C, 3A and TP17 displayed similar inhibitory activities and were capable of binding strongly to oligopeptidase B without proteolytic cleavage. The concentration of protamine needed for 50% inhibition (IC50) of oligopeptidase B was 104‐fold lower than the IC50of trypsin. Oligopeptidase B was highly sensitive to inhibition by protamines even in the presence of serum (IC50, 1 µM). These data indicate that protamines might provide information useful for the design of more specific synthetic oligopeptidase B inhibitors. Copyright © 2005 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.683

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY

摘要:

AbstractAlzheimer's disease (AD) and related dementing disorders having cognitive manifestations represent an increasing threat to public health. In the present study, the effects of a memory enhancing NLPR tetra‐peptide (MEP), huperzine A (Hup A), or a combination of the two on the cognitive abilities of brain‐lesioned mice were evaluated and compared with tacrine in the passive avoidance and$\font\ss=cmss10 scaled 1000 \hbox{\ss Y}$‐water maze tests for the acquisition and retention aspects of cognitive functions. MEP at µg kg−1doses, and Hup A or tacrine at mg kg−1doses significantly reversed the cognition deficits induced by scopolamine. For acquisition ability, it was observed that mice administered with MEP (4.0 µg kg−1) spent less time escaping onto the platform in the water maze than those treated with tacrine (1.5 mg kg−1); whereas for memory retention, tacrine‐administration resulted in a higher step‐through latency in mice at the tested dose regime. In addition, co‐administration of MEP (2.0 µg kg−1) and Hup A (0.1 mg kg−1) exhibited an additive effect resulting in considerable improvements in both acquisition and retention abilities of brain‐lesioned mice. The results demonstrated that MEP was highly efficient in the rescue of cognitive abilities of brain‐lesioned mice and in particular, the effective doses of MEP were about two orders of magnitude lower than that of tacrine, a therapeutic currently used in the treatment of AD. Moreover, MEP and Hup A were effective at reduced doses when the two were co‐administered, providing a rationale for their combined usage in the treatment of cognitive deficits. Copyright © 2005 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.682

出版商:John Wiley&Sons, Ltd.    

年代:2006

数据来源: WILEY