35 research outputs found
Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?
International audienceWhile presenting particularly interesting advantages, peptide synthesis by ball-milling was never compared to the two traditional strategies, namely peptide syntheses in solution and on solid support (solid-phase peptide synthesis, SPPS). In this study, the challenging VVIA tetrapeptide was synthesized by ball-milling, in solution, and on solid support. The three strategies were then compared in terms of yield, purity, reaction time and environmental impact. The results obtained enabled to draw some strengths and weaknesses of each strategy, and to foresee what will have to be implemented to build more efficient and sustainable peptide syntheses in the near future
Valuable Versatile Reactivity of Thiaisatoic Anhydrides: Expedient Solid-Phases Synthesis of Thieno[1,4]Diazepine-2,5-diones
International audienc
cis-Apa: A Practical Linker for the Microwave-Assisted Preparation of Cyclic Pseudopeptides via RCM Cyclative Cleavage
International audienceA new linker cis-5-aminopent-3-enoic acid (cis-Apa) was prepared for the synthesis of cyclic pseudopeptides by cyclization-cleavage by using ring-closing methatesis (RCM). We developed a new synthetic pathway for the preparation of the cis-Apa linker that was tested in the cyclizationcleavage process of different RGD peptide sequences. Different macrocyclic peptidomimetics were prepared by using this integrated microwave-assisted method, showing that the readily available cis-Apa amino acid is well adapted as a linker in the cyclization-cleavage process
Sequencing Lys-N Proteolytic Peptides by ESI and MALDI Tandem Mass Spectrometry
International audienceIn this study, we explored the MS/MS behavior of various synthetic peptides that possess a lysine residue at the N-terminal position. These peptides were designed to mimic peptides produced upon proteolysis by the Lys-N enzyme, a metalloendopeptidase issued from a Japanese fungus Grifola Frondosa that was recently investigated in proteomic studies as an alternative to trypsin digestion since a specific cleavage at the amide X-Lys chain is obtained providing N-terminal lysine peptide fragments. In contrast to tryptic peptides exhibiting a In lysine or arginine residues solely at the C-terminal position, and thus devoid of such basic amino acids within the sequence, these Lys-N proteolytic peptides can contain the highly basic arginine residue anywhere within the peptide chain. The fragmentation patterns of such sequences with ESI-QqTof and MALDI-Tof/Tof mass spectrometers commonly used in proteomic bottom-up experiments were investigated
Solid-Phase Synthesis of 4-methylcarboxy-1,4-benzodiazepine-2,5-diones
International audienceA solid-phase synthesis of 1,4-benzodiazepinone-2,5-diones is described. This new route can afford benzodiazepinone bearing a N-urethane-protected amine and a carboxylic acid function. This kind of building block is valuable as a dipeptide mimic or beta-turn mimetic, and it can be introduced in place of any amino acid in peptide synthesis. Using an "analytical probe" strategy, we optimized the synthesis of a model compound on SynPhase Lanterns. Therefore, the efficiency of several linkers was investigate
Microwave-Mediated Reduction of Disulfide Bridges with Supported (Tris(2-carboxyethyl)phosphine) as Resin-Bound Reducing Agent
International audienceWe report on the synthesis and use of a new supported reagent consisting in tris(2-carboxyethyl)phosphine (TCEP) immobilized on hydrophilic PEG based resin beads. Used in conjunction with a 5 min microwave (MW) irradiation, “supported TCEP” reduced disulfide bridges in free thiols in peptides having two or more cysteine residues. Separation of reaction products from reducing agent was easily performed by simple filtration
Solid-phase synthesis of 5-arylhistidines via a microwave-assisted Suzuki-Miyaura cross-coupling
International audienc
Ghrelin Receptor Ligands: Design and Synthesis of Pseudopeptides and Peptidomimetics.
International audienceMainly synthesized in the stomach, ghrelin is a peptide hormone which stimulates growth hormone secretion and appetite, thus promoting food intake and body-weight gain. Historically, researchers started to work on the discovery of ghrelin receptor ligands several years before the discovery of the ghrelin receptor and the hormone itself. Indeed peptides able to stimulate growth hormone secretion (growth hormone releasing peptides, GHRPs) were found while the mechanism of action and the target receptor were still unknown. Non peptidic agonists were then described (growth hormone secretagogues, GHSs) and the receptor (GHS-R1a) identified in 1996. Three years later, the natural ligand of this receptor (ghrelin) was isolated from stomach and its chemical synthesis allowed to show the physiological role of ghrelin in energy balance. In this review, we present some pseudopeptide and peptidomimetic approaches used by researchers for the design of ghrelin receptor ligands. We will start by the pioneering work of Bowers et al. on enkephalin analogues, which was the starting point for the development of an impressive number of compounds, by several of the major worldwide pharma companies. We will also describe the work achieved starting from a substance P derivative, which was one of the first peptides identified as an antagonist of the newly discovered ghrelin receptor. Then we will review the structure activity relationship study starting from the peptide ghrelin, which started with the discovery of this peptide in 1999. We will also focus on a more recent work based on macrocyclic peptidic analogues for the development of ghrelin receptor ligands
A Short SOX9 Peptide Mimics SOX9 Tumor Suppressor Activity and Is Sufficient to Inhibit Colon Cancer Cell Growth
International audienc
N- and O-acetylation of threonine residues in the context of proteomics.
International audienceThe detection of post-translational modifications (PTMs) of proteins is a matter of intensive research. Among all possible pitfalls that may lead to misidentifications, the chemical stability of modified peptides is scarcely questioned. Global proteomic studies devoted to protein acetylation are becoming popular. Thus, we were concerned about the intrinsic stability of O-acetylated peptides because of the O-N acyl transfer reactivity occurring when an amino moiety is present in the vicinity of the acylated hydroxyl group. Here, the behavior of isomeric O- and N-acetylated, N-terminal threonine-containing peptides was explored in a standard proteomic workflow. We demonstrated a strong chemical instability of O-acetylation, which prevents its detection