The Experts below are selected from a list of 29517 Experts worldwide ranked by ideXlab platform
Toshiharu Ohta - One of the best experts on this subject based on the ideXlab platform.
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novel peptidomimetics of the antifungal Cyclic Peptide rhodopeptin synthesis of mimetics and their antifungal activity
Organic Letters, 2001Co-Authors: Haruko C Kawato, Kiyoshi Nakayama, Hiroaki Inagaki, Toshiharu OhtaAbstract:Novel peptidomimetics of the antifungal Cyclic Peptide Rhodopeptin were synthesized. As with the Cyclic Peptides, the presence of all three Rhodopeptin side chains was found to be indispensable for peptidomimetic activity. We discovered new compounds exhibiting greater antifungal activity and improved physiochemical properties in comparison to the parent compounds.
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novel peptidomimetics of the antifungal Cyclic Peptide rhodopeptin design of mimetics utilizing scaffolding methodology
Organic Letters, 2001Co-Authors: Kiyoshi Nakayama, Haruko C Kawato, Hiroaki Inagaki, Toshiharu OhtaAbstract:Novel nonPeptide peptidomimetics of the antifungal Cyclic Peptide Rhodopeptin were designed utilizing hydantoin, benzimidazole, d-glucosamine, quinolone, and benzodiazepine units as scaffolds. The scaffolds were chosen on the basis of their potential to improve the physiochemical properties of the peptidomimetics as well as their ability to bear the requisite Rhodopeptin side-chain moieties with the proper three-dimensional orientation.
Franziska Thomas - One of the best experts on this subject based on the ideXlab platform.
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decoration of coiled coil Peptides with n cysteine Peptide thioesters as Cyclic Peptide precursors using copper catalyzed azide alkyne cycloaddition cuaac click reaction
Organic Letters, 2018Co-Authors: Mathis W Rink, Franziska ThomasAbstract:The development of a copper-catalyzed azide–alkyne cycloaddition (CuAAC) protocol for the decoration of coiled coils with N-cysteine Peptide thioesters as Cyclic Peptide precursors is presented. The reaction conditions include tert-butanol/PBS as the solvent and CuSO4/THPTA/ascorbate as the catalytic system. During these studies, partial formylation of N-terminal cysteine Peptides is observed. Mechanistic analysis leads to identification of the formyl source and, hence, to the development of reaction conditions, under which the undesired side reaction was suppressed.
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Decoration of Coiled-Coil Peptides with N‑Cysteine Peptide Thioesters As Cyclic Peptide Precursors Using Copper-Catalyzed Azide–Alkyne Cycloaddition (CuAAC) Click Reaction
2018Co-Authors: Mathis W Rink, Franziska ThomasAbstract:The development of a copper-catalyzed azide–alkyne cycloaddition (CuAAC) protocol for the decoration of coiled coils with N-cysteine Peptide thioesters as Cyclic Peptide precursors is presented. The reaction conditions include tert-butanol/PBS as the solvent and CuSO4/THPTA/ascorbate as the catalytic system. During these studies, partial formylation of N-terminal cysteine Peptides is observed. Mechanistic analysis leads to identification of the formyl source and, hence, to the development of reaction conditions, under which the undesired side reaction was suppressed
Sébastien Perrier - One of the best experts on this subject based on the ideXlab platform.
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hierarchical self assembled photo responsive tubisomes from a Cyclic Peptide bridged amphiphilic block copolymer
Angewandte Chemie, 2020Co-Authors: Jie Yang, Julia Y. Rho, Edward D. H. Mansfield, Jiinn Song, Qiao Song, Stephen C L Hall, Megan Sambrook, Feihe Huang, Sébastien PerrierAbstract:Typically, the morphologies of the self-assembled nanostructures from block copolymers are limited to spherical micelles, wormlike micelles and vesicles. Now, a new generation of materials with unique shape and structures, cylindrical soft matter particles (tubisomes), are obtained from the hierarchical self-assembly of Cyclic Peptide-bridged amphiphilic diblock copolymers. The capacity of obtained photo-responsive tubisomes as potential drug carriers is evaluated. The supramolecular tubisomes pave an alternative way for fabricating polymeric tubular structures, and will expand the toolbox for the rational design of functional hierarchical nanostructures.
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probing the dynamic nature of self assembling Cyclic Peptide polymer nanotubes in solution and in mammalian cells
Advanced Functional Materials, 2018Co-Authors: Julia Y. Rho, Johannes C. Brendel, Liam R. Macfarlane, Edward D. H. Mansfield, Raoul Peltier, Sarah E. Rogers, Matthias Hartlieb, Sébastien PerrierAbstract:Self-assembling Cyclic Peptide–polymer nanotubes have emerged as a fascinating supramolecular system, well suited for a diverse range of biomedical applications. Due to their well-defined diameter, tunable Peptide anatomy, and ability to disassemble in situ, they have been investigated as promising materials for numerous applications including biosensors, antimicrobials, and drug delivery. Despite this continuous effort, the underlying mechanisms of assembly and disassembly are still not fully understood. In particular, the exchange of units between individual assembled nanotubes has been overlooked so far, despite its knowledge being essential for understanding their behavior in different environments. To investigate the dynamic nature of these systems, Cyclic Peptide–polymer nanotubes are synthesized, conjugated with complementary dyes, which undergo a Forster resonance energy transfer (FRET) in close proximity. Model conjugates enable to demonstrate not only that their self-assembly is highly dynamic and not kinetically trapped, but also that the self-assembly of the conjugates is strongly influenced by both solvent and concentration. Additionally, the versatility of the FRET system allows studying the dynamic exchange of these systems in mammalian cells in vitro using confocal microscopy, demonstrating the exchange of subunits between assembled nanotubes in the highly complex environment of a cell.
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structure elucidation and control of Cyclic Peptide derived nanotube assemblies in solution
Chemical Science, 2013Co-Authors: Robert Chapman, Katrina A Jolliffe, Ming Liang Koh, Gregory G Warr, Sébastien PerrierAbstract:We describe the solution assembly of polymer–Cyclic Peptide conjugates into nanotubes, by direct in situ measurements. The conjugates were assembled by exploiting the β-sheet assembly of the alt(D,L) Cyclic octaPeptide core. The conjugated polymer permits solubilization of the Peptide and the resulting nanotubes, thus allowing for the first time the direct study of the assembly mechanism of this system. The resulting materials present unique properties for a wide range of applications. We find that the polymer can act to both shield the Peptide core from the solvent and to put strain on the Peptide core through steric repulsions. By controlling both the solvent mixture and the length of the polymer, control over the length of the resulting nanotubes can be obtained. In addition, monitoring the assembly with temperature allows the strength of the assembly to be probed, adding evidence for a co-operative mechanism of assembly. Finally, selective deuteration of the polymer component in SANS analyses leads to the precise measurement of the nanotubes core dimensions, and by cross-linking the polymeric shell, the structure of the nanotubes in solution are confirmed by transmission electron microscopy (TEM). This study establishes the fundamentals needed for the design and control of these new materials.
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design and properties of functional nanotubes from the self assembly of Cyclic Peptide templates
Chemical Society Reviews, 2012Co-Authors: Robert Chapman, Maarten Danial, Katrina A Jolliffe, Sébastien PerrierAbstract:β-Sheet forming self assembling Cyclic Peptides offer a versatile scaffold for the construction and control of hydrogen-bonded nanotube assemblies. These structures have major advantages over other nanoscale tubular structures, including sub-nanometer control over the internal diameter, and the ability to control internal and external chemical functionality. This Tutorial Review presents an overview of nanotubes derived from this class of Cyclic Peptides. The design rationale for functional nanotubes based on Cyclic Peptide ring size and chemical functionality is discussed. Additionally, we highlight the recent expansion of the nanotube toolbox through conjugation of (macro)molecules to the Cyclic Peptides. These provide additional functionality and control nanotube dimensions that could potentially prove beneficial in future applications.
Ali Tavassoli - One of the best experts on this subject based on the ideXlab platform.
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SICLOPPS Cyclic Peptide libraries in drug discovery
Current Opinion in Chemical Biology, 2017Co-Authors: Ali TavassoliAbstract:Cyclic Peptide libraries have demonstrated significant potential when employed against challenging targets such as protein–protein interactions. While a variety of methods for library generation exist, genetically encoded libraries hold several advantages over their chemically synthesized counterparts; they are more readily accessible and allow straightforward hit deconvolution. One method for the intracellular generation of such libraries is split-intein circular ligation of Peptides and proteins (SICLOPPS). Here we detail and discuss the deployment of SICLOPPS libraries for the identification of Cyclic Peptide inhibitors of a variety of targets.
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Traceless Production of Cyclic Peptide Libraries in E. coli
2016Co-Authors: Jaime E. Townend, Ali TavassoliAbstract:Split intein circular ligation of Peptides and proteins (SICLOPPS) is a genetically encoded method for the intracellular production of Cyclic Peptide libraries of around 100 million (108) members that utilizes the Synechocystis sp PCC6803 (Ssp) DnaE split inteins. However, Ssp inteins are relatively slow splicing and intolerant of amino acid variation around the splice junction, potentially limiting the utility and composition of SICLOPPS libraries. In contrast, Nostoc punctiforme (Npu) DnaE split inteins not only splice significantly faster, they are also much more tolerant of amino acid variation around their splice junctions. Here, we report the use of engineered Npu inteins in SICLOPPS for the generation of Cyclic Peptide libraries and Cyclic proteins. Despite their superior splicing characteristics, however, we observed a high level of toxicity from the Npu SICLOPPS constructs in E. coli. The observed toxicity was overcome though incorporation of an SsrA tag to target the spliced Npu inteins to the ClpXP complex for degradation. The resulting traceless Npu SICLOPPS inteins showed no toxicity to E. coli, demonstrating their potential for the production of Cyclic Peptide libraries for use in a variety of high-throughput screens
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inhibition of hiv budding by a genetically selected Cyclic Peptide targeting the gag tsg101 interaction
ACS Chemical Biology, 2008Co-Authors: Ali Tavassoli, Stephen J Benkovic, Jongsik Gam, Hui Pan, Stanley N CohenAbstract:The egress of HIV particles from virus-infected cells is accomplished by the recruitment of proteins that normally mediate host cell endocytic functions. This process requires interaction of the HIV Gag protein with the host protein TSG101 (tumor susceptibility gene 101). Here, we report the use of a bacterial reverse two-hybrid system to identify Cyclic Peptides that interfere with the Gag−TSG101 interaction and the finding that a five amino acid Peptide discovered by this approach can disrupt the interaction and consequently inhibit HIV egress. The inhibiting molecule, which was selected from a Cyclic Peptide library containing ∼3.2 × 106 members, differs in primary sequence from the interacting sites of either TSG101 or Gag. Addition of Cyclic Peptide tagged with an HIV Tat sequence, which previously has been shown to enhance protein translocation across plasma membranes, to cultured human cells inhibited the production of virus-like particles (VLPs) by these cells (IC50 of 7 μM), and this inhibition o...
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split intein mediated circular ligation used in the synthesis of Cyclic Peptide libraries in e coli
Nature Protocols, 2007Co-Authors: Ali Tavassoli, Stephen J BenkovicAbstract:Recent advances in chemical biology and the advantages presented by in vivo screening have highlighted the need for a robust and flexible biologically synthesized small-molecule library. Herein we describe a method for the biosynthesis of Cyclic Peptide libraries of up to 108 members in Escherichia coli using split-intein circular ligation of Peptides and proteins (SICLOPPS). The method utilizes split-intein chemistry to cyclize randomized Peptide sequences. The Cyclic Peptide library can potentially be of any size and the Peptide itself may contain unlimited random residues. However, the library size is limited by the transformation efficiency of E. coli and random residues are generally limited to five, but additional amino acids can be used in the Cyclic Peptide backbone, varying the structure and ring size of the Cyclic Peptide. SICLOPPS libraries have been combined with a bacterial reverse two-hybrid system in our labs and used in the identification of inhibitors of several protein–protein interactions. This protocol is expected to take around 3–4 weeks to implement.
Peta J Harvey - One of the best experts on this subject based on the ideXlab platform.
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development of novel melanocortin receptor agonists based on the Cyclic Peptide framework of sunflower trypsin inhibitor 1
Journal of Medicinal Chemistry, 2018Co-Authors: Thomas Durek, Philipp M Cromm, Andrew M White, Christina I Schroeder, Quentin Kaas, Joachim Weidmann, Abdullah Ahmad A H Fuaad, Olivier Cheneval, Peta J HarveyAbstract:Ultrastable Cyclic Peptide frameworks offer great potential for drug design due to their improved bioavailability compared to their linear analogues. Using the sunflower trypsin inhibitor-1 (SFTI-1) Peptide scaffold in combination with systematic N-methylation of the grafted pharmacophore led to the identification of novel subtype selective melanocortin receptor (MCR) agonists. Multiple biCyclic Peptides were synthesized and tested toward their activity at MC1R and MC3–5R. Double N-methylated compound 18 showed a pKi of 8.73 ± 0.08 (Ki = 1.92 ± 0.34 nM) and a pEC50 of 9.13 ± 0.04 (EC50 = 0.75 ± 0.08 nM) at the human MC1R and was over 100 times more selective for MC1R. Nuclear magnetic resonance structural analysis of 18 emphasized the role of Peptide bond N-methylation in shaping the conformation of the grafted pharmacophore. More broadly, this study highlights the potential of Cyclic Peptide scaffolds for epitope grafting in combination with N-methylation to introduce receptor subtype selectivity in the ...
