Cyclic peptides represent a popular class of macrocyclic drug candidates and therefore their solid phase synthesis has attracted much attention. In this contribution we present an efficient method... Show moreCyclic peptides represent a popular class of macrocyclic drug candidates and therefore their solid phase synthesis has attracted much attention. In this contribution we present an efficient method of side-chain anchoring for ornithine and lysine residues to be used in the standard Fmoc-based synthesis of cyclic peptides via on-resin cyclization. We demonstrate that the side chain of ornithine and lysine protected with N-Bocgroup can efficiently be converted to the isocyanate which is then immobilized on Wang-type resin in almost quantitative yield. We further show the synthesis of four biologically active cyclic peptides employing the side chain ornithine anchoring. Our method is at least on a par with the previously reported methodologies in terms of yield and the purity of the final products and is arguably operationally more straightforward. Show less
Correction for ‘Glycosylated cyclophellitol-derived activity-based probes and inhibitors for cellulases’ by Casper de Boer et al., RSC Chem. Biol., 2020, 1, 148–155, DOI: 10.1039/d0cb00045k.The aut... Show moreCorrection for ‘Glycosylated cyclophellitol-derived activity-based probes and inhibitors for cellulases’ by Casper de Boer et al., RSC Chem. Biol., 2020, 1, 148–155, DOI: 10.1039/d0cb00045k.The authors regret that an incorrect PDB code for the structure of the Humicola insolens Cel7B with β–1,4 glucosyl cyclophellitol was given in the Data deposition section of the original article. The correct PDB code is 6YOZ.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers. Show less
Cyclic peptides are investigated as a platform to induce different orientations between various ligands. Through click chemistry, a variety of Toll-like receptor ligands can be attached to the... Show moreCyclic peptides are investigated as a platform to induce different orientations between various ligands. Through click chemistry, a variety of Toll-like receptor ligands can be attached to the cyclic peptides, which are based on gramicidin S. Show less
Self-adjuvanting vaccines, wherein an antigenic peptide is covalently bound to an immunostimulating agent, have been shown to be promising tools for immunotherapy. Synthetic Toll-like receptor (TLR... Show moreSelf-adjuvanting vaccines, wherein an antigenic peptide is covalently bound to an immunostimulating agent, have been shown to be promising tools for immunotherapy. Synthetic Toll-like receptor (TLR) ligands are ideal adjuvants for covalent linking to peptides or proteins. We here introduce a conjugation-ready TLR4 ligand, CRX-527, a potent powerful lipid A analogue, in the generation of novel conjugate-vaccine modalities. Effective chemistry has been developed for the synthesis of the conjugation-ready ligand as well as the connection of it to the peptide antigen. Different linker systems and connection modes to a model peptide were explored, and in vitro evaluation of the conjugates showed them to be powerful immune-activating agents, significantly more effective than the separate components. Mounting the CRX-527 ligand at the N-terminus of the model peptide antigen delivered a vaccine modality that proved to be potent in activation of dendritic cells, in facilitating antigen presentation, and in initiating specific CD8(+) T-cell-mediated killing of antigen-loaded target cells in vivo. Synthetic TLR4 ligands thus show great promise in potentiating the conjugate vaccine platform for application in cancer vaccination. Show less
Self-adjuvanting vaccines, wherein an antigenic peptide is covalently bound to an immunostimulating agent, have been shown to be promising tools for immunotherapy. Synthetic Toll-like receptor (TLR... Show moreSelf-adjuvanting vaccines, wherein an antigenic peptide is covalently bound to an immunostimulating agent, have been shown to be promising tools for immunotherapy. Synthetic Toll-like receptor (TLR) ligands are ideal adjuvants for covalent linking to peptides or proteins. We here introduce a conjugation-ready TLR4 ligand, CRX-527, a potent powerful lipid A analogue, in the generation of novel conjugate-vaccine modalities. Effective chemistry has been developed for the synthesis of the conjugation-ready ligand as well as the connection of it to the peptide antigen. Different linker systems and connection modes to a model peptide were explored, and in vitro evaluation of the conjugates showed them to be powerful immune-activating agents, significantly more effective than the separate components. Mounting the CRX-527 ligand at the N-terminus of the model peptide antigen delivered a vaccine modality that proved to be potent in activation of dendritic cells, in facilitating antigen presentation, and in initiating specific CD8+ T-cell-mediated killing of antigen-loaded target cells in vivo. Synthetic TLR4 ligands thus show great promise in potentiating the conjugate vaccine platform for application in cancer vaccination. Show less
