- Compatibility between the cysteine-cyclopentenedione reaction and the copper(i)-catalyzed azide-alkyne cycloaddition
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The cysteine-cyclopentenedione reaction can be combined with the copper(i)-catalyzed azide-alkyne cycloaddition provided that the former is carried out first. If not, the azide and the cyclopentenedione undergo a 1,3-dipolar cycloaddition, which furnishes triazole-containing compounds and products resulting from nitrogen loss. Both of these products were fully characterized. Attempts to obtain either of them as the main compound or to drive the reaction nearly to completion were unsuccessful, which points to the azide-cyclopentenedione reaction as not being useful for bioconjugation.
- Agramunt, Jordi,Saltor, Laia,Pedroso, Enrique,Grandas, Anna
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- Synthesis of chemically-tethered amyloid-β segment trimer possessing amyloidogenic properties
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As amyloid-β (Aβ) undergoes dynamic aggregation, it is impossible to isolate ('hook') the transient Aβ oligomer in an assembly state-pure form (e.g., sole Aβ dimer, trimer, tetramer, etc.). Obtaining such a pure Aβ oligomer would allow us to establish an in vitro system to perform a more detailed investigation of the pathogenic properties of the oligomer. A chemically-tethered Aβ oligomer, constructed only by covalent bonds, could satisfy this demand. Here we designed a chemically-tethered trimer of a pathogenic Aβ fragment (Aβ25-35) (1) and successfully generated it in situ from its precursor (4), a water-soluble and non-aggregative O-acyl isopeptide of 1, in neutral aqueous media. Chemically-tethered 1 possessed stronger amyloidogenic properties, that is, potential for β-sheet structure, fibril formation, and cytotoxicity, than the corresponding monomer Aβ25-35 (6). Trimerization of Aβ25-35 sequence might affect both the aggregative properties and cytotoxicity, based on the present results. This work opens the door for chemical synthesis of oligomers bigger than trimers in an assembly state-pure form, allowing for identification of the most toxic Aβ oligomer.
- Shinoda, Kiyomichi,Sohma, Youhei,Kanai, Motomu
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- Synthesis of peptide homo- and heterodimers as potential mimics of platelet-derived growth factor BB
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Pericyte loss is correlated with blood-brain barrier leakage in neurological disorders such as Alzheimer's disease. The platelet-derived growth factor receptor β (PDGFRβ)/platelet-derived growth factor BB (PDGF-BB) signalling pathway is key to the regulation of pericyte survival and proliferation. A series of peptide dimers mimicking the ligand PDGF-BB were prepared in the hope of stimulating PDGFRβ internalisation and activation of this pathway. Copper-catalysed azide-alkyne cycloaddition of peptide monomers with PEGylated linkers of varying length afforded the desired peptide dimers. Evaluation of the peptide dimers in human brain pericyte assays revealed no effect on PDGFRβ internalisation nor cell proliferation at concentrations 10 μM. The peptide dimers also did not act as antagonists at PDGFRβ at concentrations 10 μM.
- Stubbing, Louise A.,Kaur, Harveen,Feng, Sheryl X.,Aalderink, Miranda,Dragunow, Michael,Brimble, Margaret A.
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- Stepwise triple-click functionalization of synthetic peptides
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The increasing popularity of peptides as promising molecular scaffolds for biomedical applications and as valuable biochemical probes makes new methods allowing for their modification highly desirable. We describe herein an optimized protocol based on a sequence of CuAAC click reactions and selective deprotection steps, which leads to an efficient multi-functionalization of synthetic peptides. The methodology has been successfully applied to the construction of defined heteroglycopeptides and fluorophore-quencher-containing probes for proteases. The developed chemistry thus represents an important addition to the available toolbox of methods enabling efficient postsynthetic modification of peptides. The commercial availability of numerous azide probes further greatly extends the application potential of the described methodology.
- Kovalová, Anna,Pohl, Radek,Vrabel, Milan
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supporting information
p. 5960 - 5964
(2018/09/06)
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- OPTICAL PROBE FOR THROMBIN
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Optical probes are presented, the probes comprising a first probe element, and a second probe element connected to a core. The first probe element comprises a first fluorophore connected to a first quencher by a first cleavable linker. The second probe el
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Page/Page column 37
(2016/10/11)
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