The strain-promoted "double-click" (SPDC) reaction using Sondheimer diyne, a novel convergent method conjugating three molecules spontaneously, has enabled us to readily modify an azido-biomolecule with a small reporter azido-molecule.
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http://dx.doi.org/10.1039/c0ob00003e | DOI Listing |
Bioconjug Chem
November 2022
Department of Radiology, Biomedical Research Imaging Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
An efficient modular strategy for rapid assembly of positron emission tomography (PET) agents has been developed. The use of a sequential, rapid, and selective double-click reaction allows for a combinatorial approach to the cross-linking of positron emitter-bearing prosthetic groups with various ligands. The strain-promoted azide alkyne cyclization (SPAAC) coupling of F-labeled azide synthon with MC-DIBOD, a cyclooctadiyne with one of the triple bonds caged as a cyclopropenone moiety, produces a stable intermediate.
View Article and Find Full Text PDFBioorg Med Chem
July 2021
Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan; Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia.
An amino group at side chain of lysine residue can be targeted for protein modification because of the convenience for covalent bond formation. We have achieved an efficient protein modification by utilizing amine-clickable 6π-azaelectrocyclization, termed RIKEN click reaction recently, which enabled direct click labeling of protein without any introduction of specific functional groups such as alkynes and azides. On the basis of the RIKEN click reaction, we established the double click labeling method.
View Article and Find Full Text PDFMethods Enzymol
June 2021
Department of Chemistry, McGill University, QC, Canada.
Bioorthogonal ligation reactions are powerful tools for characterizing DNA metabolism, DNA-protein binding interactions, and they even provide new leads for therapeutic strategies. Nucleoside analogs can deliver bioorthogonal functional groups into chromatin via cellular metabolic pathways, however, insufficient phosphorylation by endogenous kinases often limits the efficiency of their incorporation. Even when successfully metabolized into biopolymers, steric hindrance of the modified nucleotide by chromatin can inhibit subsequent click reactions.
View Article and Find Full Text PDFACS Omega
January 2020
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.
The Sondheimer dialkyne reagent has previously been employed in strain-promoted double-click cycloadditions with bis-azide peptides to generate stapled peptide inhibitors of protein-protein interactions. The substituted variants of the Sondheimer dialkyne can be used to generate functionalized stapled peptide inhibitors with improved biological properties; however, this remains a relatively underdeveloped field. Herein, we report the synthesis of new substituted variants of Sondheimer dialkyne and their application in the stapling of p53-based diazido peptides to generate potent stapled peptide-based inhibitors of the oncogenic p53-MDM2 interaction.
View Article and Find Full Text PDFChem Commun (Camb)
September 2019
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
A novel PtIV triazolato azido complex [3]-[N1,N3] has been synthesised via a strain-promoted double-click reaction (SPDC) between a PtIV azido complex (1) and the Sondheimer diyne (2). Photoactivation of [3]-[N1,N3] with visible light (452 nm) in the presence of 5'-guanosine monophosphate (5'-GMP) produced both PtIV and PtII 5'-GMP species; EPR spectroscopy confirmed the production of both azidyl and hydroxyl radicals. Spin-trapping of photogenerated radicals - particularly hydroxyl radicals - was significantly reduced in the presence of 5'-GMP.
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