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Peptide Amides (peptide + amide)
Selected AbstractsThe design of a new potent and selective ligand for the orphan bombesin receptor subtype 3 (BRS3)JOURNAL OF PEPTIDE SCIENCE, Issue 3 2005Robert G. Boyle Abstract Extensive SAR studies on the unselective BRS3 agonist, [H-D-Phe6,,-Ala11,Phe13,Nle14]-bombesin-(6-14)-nonapeptide amide, have highlighted structural features important for BRS3 activity and have provided guidance as to the design of selective agonists. A radically modified heptapeptide agonist, maintaining only the Trp-Ala moiety of the parent [H-D-Phe6,,Ala11,Phe13,Nle14]-peptide amide, and with a very different carboxyl terminal region, has been produced which was potent at BRS3 and essentially had no NMB or GRP receptor activity. Its structure is Ac-Phe-Trp-Ala-His(,Bzl)-Nip-Gly-Arg-NH2. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] New indolicidin analogues with potent antibacterial activity,CHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2004T.S. Ryge Abstract:, Indolicidin is a 13-residue antimicrobial peptide amide, ILPWKWPWWPWRR-NH2, isolated from the cytoplasmic granules of bovine neutrophils. Indolicidin is active against a wide range of microorganisms and has also been shown to be haemolytic and cytotoxic towards erythrocytes and human T lymphocytes. The aim of the present paper is two-fold. First, we examine the importance of tryptophan in the antibacterial activity of indolicidin. We prepared five peptide analogues with the format ILPXKXPXXPXRR-NH2 in which Trp-residues 4,6,8,9,11 were replaced in all positions with X = a single non-natural building block; N -substituted glycine residue or nonproteinogenic amino acid. The analogues were tested for antibacterial activity against both Staphylococcus aureus American type culture collection (ATCC) 25923 and Escherichia coli ATCC 25922. We found that tryptophan is not essential in the antibacterial activity of indolicidin, and even more active analogues were obtained by replacing tryptophan with non-natural aromatic amino acids. Using this knowledge, we then investigated a new principle for improving the antibacterial activity of small peptides. Our approach involves changing the hydrophobicity of the peptide by modifying the N-terminus with a hydrophobic non-natural building block. We prepared 22 analogues of indolicidin and [Phe4,6,8,9,11] indolicidin, 11 of each, carrying a hydrophobic non-natural building block attached to the N-terminus. Several active antibacterial analogues were identified. Finally, the cytotoxicity of the analogues against sheep erythrocytes was assessed in a haemolytic activity assay. The results presented here suggest that modified analogues of antibacterial peptides, containing non-natural building blocks, are promising lead structures for developing future therapeutics. [source] N -Tetrachlorophthaloyl (TCP) Protection for Solid-Phase Peptide SynthesisEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2004Esther Cros Abstract The N -tetrachlorophthaloyl-(TCP-)amino protecting group has been evaluated for use in solid-phase peptide synthesis. The TCP group was unaffected by exposure to either piperidine or N,N -diisopropylethylamine (DIEA), which suggests compatibility with both Fmoc and Boc solid-phase synthesis protocols. Quantitative TCP removal was achieved by treatment with hydrazine/DMF (3:17) at 35 °C for 30 min or with ethylenediamine/DMF (1:200) at 50 °C for 30 min. Several C-terminal peptide amides were synthesized successfully by following protocols that use hydrazine/DMF (3:17) at 40 °C for 1 h for repetitive deprotection. Treatment of TCP-amines with methylamine or with diamines did not give the corresponding amines (deprotected), but rather the appropriate N,N, -disubstituted tetrachlorophthalamides, which corresponds to a single ring-opening step. This observation was harnessed to prepare linear and macrocyclic peptide,arene hybrids based on the mild reaction of the parent TCP compound with 1,3-diaminopropane/DMF (1:49) at 25 °C for 5 min. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Benzhydrylamine linker grafting: a strategy for the improved synthesis of C -terminal peptide amides,JOURNAL OF PEPTIDE SCIENCE, Issue 10 2010Dianne Alewood Abstract The standard p -MBHA resin used during Boc-chemistry synthesis of peptides carrying C -terminal carboxamides is compromised by batch-to-batch variations in its performance. This can cause artificially ,difficult' couplings during peptide chain assembly, which may ultimately lead to failed syntheses given the inability to achieve acceptable coupling yields. To overcome these problems, we have developed a new approach by grafting a functionalized benzhydrylamine linker onto well-characterized and well-performing PAM resins. We combine optimized Boc-chemistry, high-performing PAM resins and new benzhydrylamine-based linkers to achieve improved syntheses of peptide amides. Here we present the synthesis of two new benzhydrylamine linkers and their attachment to selected PAM resins. This novel solid support was evaluated through the synthesis of selected ,difficult' conotoxins and monitoring the coupling efficiency using quantitative ninhydrin assay. The results show a superior performance of the novel linker solid support compared to the standard p -MBHA resins routinely used. In summary, we describe an alternative linker-resin system that allows improved access to C -terminal amide peptides employing Boc/Bzl chemistry. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. [source] Crystallization and preliminary X-ray data of the recombinant peptide amidase from Stenotrophomonas maltophiliaACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2002Sebastian Neumann The peptide amidase from Stenotrophomonas maltophilia selectively hydrolyses the C-terminal amide bond in peptide amides. Crystals have been obtained by sitting-drop vapour diffusion from solution containing polyethylene glycol (PEG) 6000, HEPES pH 7.5, glycerine and sodium azide (NaN3). The crystals belong to the monoclinic space group P21, with unit-cell parameters a = 74.18, b = 62.60, c = 101.91,Å, , = 90°. X-ray data from these crystals diffracted at the European Synchrotron Radiation Facility (ESRF, France) ID14-1 beamline to 1.4,Å. [source] Chemotactic activity of oligopeptides containing an EWS motif on Tetrahymena pyriformis: the effect of amidation of the C-terminal residueCELL BIOCHEMISTRY AND FUNCTION, Issue 2 2003László Köhidai Abstract Chemotactic properties of 3,7-mer peptides containing an EWS motive and their peptide amides synthesized and characterized by us were investigated in Tetrahymena pyriformis GL model. Analysis of the peptide acids shows that SEWS possesses exceptionally strong (660%±21; 430%±18) chemoattractant ability at 10,12 and 10,11m respectively. The shorter peptide (EWS) possesses chemorepellent activity, while longer peptides display neutral (WSEWS) or moderate chemoattractant (EWSEWS and GEWSEWS) chemotactic ability. Amidation of the C-terminus can significantly modify the character of peptides: it points to the conclusion that a free ,-COOH group at this position is required for the high efficiency of SEWS, while in the shorter (EWS) and longer peptides (WSEWS and EWSEWS) amidation can result in chemoattractant ligands. Evaluation of the structure,function relationship of these compounds establishes the significance of Glu (E) with its high surface-exposed area and negatively-charged side chain. The high discriminative ability and good chemotactic responsiveness of Tetrahymena support the theory that a chemotactic signalling mechanism working in higher levels of phylogeny is a well conserved and inducible one even in protozoa. Copyright © 2002 John Wiley & Sons, Ltd. [source] | |||||||||||||