Project description:Pathological levels of oxidative stress (OS) have been implicated in many diseases including diabetes mellitus, neurodegenerative diseases, inflammatory diseases, atherosclerosis, and cancer. Studies of oxidative stress are however complicated by the low concentration of oxidation products. To resolve this problem, we tested a new derivative of aminoadipic semialdehyde (Fmoc-Aea-OH) in the solid-phase synthesis of carbonylated peptides. We prepared a series of peptides with free and acetylated N-terminal amino groups using the Fmoc-Aea-OH reagent. LC-MS, ESI-MS, and MS/MS spectra confirmed the sequences of the modified peptides, although the LC-MS and ESI-MS spectra were dominated by signals corresponding to dehydration products. NMR studies of acetylated products revealed that the dominant product formed in this reaction contains a 1,2,3,4-tetrahydropyridine-2-carboxylic acid residue. Another side reaction in this system was the cleavage of the amide bond between the Aea residue and the amino acid moiety preceding it resulting in the formation of a side product with a six-membered ring at the N-terminus (2,3,4,5-tetrahydropyridine-2-carboxylic acid residue). We found that, depending on the peptide sequence, one of those side products is predominant. Our work suggests new methods for the solid-state synthesis of peptides containing unnatural amino acids.
Project description:A methodology for the solid-phase synthesis of biaryl bicyclic peptides containing a Phe-Phe, a Phe-Tyr or a Tyr-Tyr motif has been devised. This approach comprises two key steps. The first one involves the cyclization of a linear peptidyl resin containing the corresponding halo- and boronoamino acids via a microwave-assisted Suzuki-Miyaura cross coupling. This step is followed by the macrolactamization of the resulting biaryl monocyclic peptidyl resin leading to the formation of the expected biaryl bicyclic peptide. This study provides the first solid-phase synthesis of this type of bicyclic compounds being amenable to prepare a diversity of synthetic or natural biaryl bicyclic peptides.
Project description:We report a photolabile linker compatible with Fmoc solid phase peptide synthesis and Cu(I)-catalyzed alkyne-azide cycloaddition that allows photochemical cleavage to afford a C-terminal peptide fragment with a native amino terminus.
Project description:Photochemical reactions can cause significant transformations of manufactured nanomaterials in sunlit environments. While transformations of inorganic nanoparticles (NPs) have been investigated extensively, less attention has been focused on the direct impact of aqueous photochemical reactions on adsorbed organic macromolecules that form the NP corona and strongly influence the surface interactions and reactivity that affect NP transport, fate, and toxicity. Here, we assess the transformations of methoxy polyethylene glycol thiol (mPEGSH) coatings on gold NPs (AuNPs) under controlled UV irradiation. A decrease in the adsorbed layer thickness of polymer was observed within 24 h of UV irradiation, resulting in increased susceptibility of the transformed NPs to aggregation. Surface chemistry analyses, including X-ray photoelectron spectroscopy (XPS), showed loss of the ether groups but persistence of reduced S on the AuNP surface, indicative of a chain scission mechanism yielding different NP surface properties from that of either the initial PEGylated AuNP or the citrate-stabilized AuNP prior to coating with mPEGSH. The transformation of the chemisorbed polymer was compared to that of dissolved mPEGSH in the presence and absence of the Au NPs, as evaluated by liquid chromatography - mass spectrometry (LC-MS). In contrast to the NP-adsorbed coating, the primary observed transformation of the dissolved mPEGSH was thiol oxidation to disulfides without extensive chain scission. This study demonstrates that transformations of adsorbed macromolecular coatings must be considered to accurately predict NP attachment behavior, and hence transport, in environmental systems. Because the corona transformation was not predictable from that of the dissolved polymer, direct NP surface characterization is required to discern the fundamental reactions involved in the photochemical transformation of coatings after sorption to the NP surface.
Project description:The late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties facilitates downstream diversification and leads to changes in their biological properties. Here, the synthesis of two hydroxy-bearing allyl pyrophosphates is described. A chemoenzymatic method is demonstrated which uses a promiscuous indole prenyltransferase enzyme to install a dual reactive hydroxy-bearing allyl moiety directly on the indole ring of tryptophan-containing peptides. This is the first report of late-stage indole modifications with this reactive group.
Project description:Artificial photosynthesis relies on the availability of semiconductors that are chemically stable and can efficiently capture solar energy. Although metal oxide semiconductors have been investigated for their promise to resist oxidative attack, materials in this class can suffer from chemical and photochemical instability. Here we present a methodology for evaluating corrosion mechanisms and apply it to bismuth vanadate, a state-of-the-art photoanode. Analysis of changing morphology and composition under solar water splitting conditions reveals chemical instabilities that are not predicted from thermodynamic considerations of stable solid oxide phases, as represented by the Pourbaix diagram for the system. Computational modelling indicates that photoexcited charge carriers accumulated at the surface destabilize the lattice, and that self-passivation by formation of a chemically stable surface phase is kinetically hindered. Although chemical stability of metal oxides cannot be assumed, insight into corrosion mechanisms aids development of protection strategies and discovery of semiconductors with improved stability.
Project description:This report discloses the photochemical homolytic cleavage of iodine azide after its formation following release from polymer-bound bisazido iodate(I) anions. A series of radical reactions are reported including the 1,2-functionlization of alkenes and the unprecedented chemoselective oxidation of secondary alcohols in the presence of primary alcohols.
Project description:The compatibility of photochemistry with solid-phase peptide synthesis is demonstrated via photochemical hydroalkylation to form C(sp3)-C(sp3) bonds between on-resin Giese acceptors and redox-active esters. Both iridium-based photocatalysts and Hantszch ester led to high yields, with final reaction conditions producing full conversions within 30 min under ambient conditions. The chemistry is compatible with a broad range of peptide side chains, redox-active esters, and resin. These conditions represent the first example of photochemical peptide modifications on resin.
Project description:Here we describe the application of photochemical decarboxylative arylation as a late-stage functionalization reaction for peptides. The reaction uses redox-active esters of aspartic acid and glutamic acid on the solid phase to provide analogues of aromatic amino acids. By using aryl bromides as arylation reagents, a wide variety of amino acids can be accessed without having to synthesize them individually in solution. The reaction is compatible with proteinogenic amino acids and was used to perform a structure-activity relationship study of a PRMT5 binding peptide.
Project description:Isolated perfused rat kidneys removed considerable quantities of glycyltyrosine, glycylhydroxyproline, tetraglycine and prolylhydroxyproline from the perfusate. The component amino acids are released into the perfusate and, in the case of the glycine-containing peptides, there is increased synthesis of serine. Removal of peptides was more than could be accounted for on the basis of filtration, so antiluminal metabolism is indicated. Metabolism of such peptides by the kidney may contribute to renal serine synthesis in vivo.