847490-49-7Relevant articles and documents
Selective Photoaffinity Probe That Enables Assessment of Cannabinoid CB2 Receptor Expression and Ligand Engagement in Human Cells
Soethoudt, Marjolein,Stolze, Sara C.,Westphal, Matthias V.,Van Stralen, Luuk,Martella, Andrea,Van Rooden, Eva J.,Guba, Wolfgang,Varga, Zoltan V.,Deng, Hui,Van Kasteren, Sander I.,Grether, Uwe,Ijzerman, Adriaan P.,Pacher, Pal,Carreira, Erick M.,Overkleeft, Herman S.,Ioan-Facsinay, Andreea,Heitman, Laura H.,Van Der Stelt, Mario
, p. 6067 - 6075 (2018)
Chemical tools and methods that report on G protein-coupled receptor (GPCR) expression levels and receptor occupancy by small molecules are highly desirable. We report the development of LEI121 as a photoreactive probe to study the type 2 cannabinoid receptor (CB2R), a promising GPCR to treat tissue injury and inflammatory diseases. LEI121 is the first CB2R-selective bifunctional probe that covalently captures CB2R upon photoactivation. An incorporated alkyne serves as ligation handle for the introduction of reporter groups. LEI121 enables target engagement studies and visualization of endogenously expressed CB2R in HL-60 as well as primary human immune cells using flow cytometry. Our findings show that strategically functionalized probes allow monitoring of endogenous GPCR expression and engagement in human cells using tandem photoclick chemistry and hold promise as biomarkers in translational drug discovery.
Spontaneous Single-Crystal-to-Single-Crystal Evolution of Two Cross-Laminated Polymers
Athiyarath, Vignesh,Sureshan, Kana M.
, p. 612 - 617 (2018/12/13)
Two cases of spontaneous evolution of monomers to linear polymers having novel cross-laminated topology are reported. We synthesized two peptide monomers N3-Gly-Gly-NH-CH2-CCH and N3-Gly-Gly-Gly-CH2-CCH and solved their crystal structures by single-crystal X-ray diffraction. They adopt H-bonded crisscrossed layered packing in their crystals such that: (a) the monomers are aligned head-to-tail in 1D-chain-like arrays and parallel arrangement of such arrays forms a layer; (b) the proximally placed azide and alkyne motifs are in an orientation apt for their regiospecific cycloaddition; (c) each monomer having x peptide bonds is H-bonded with 2x monomers disposed in intersecting arrangement, which pre-organize 1D-chain-like arrays in adjacent layers in perpendicular orientation. These crystals underwent spontaneous single-crystal-to-single-crystal (SCSC) polymerization via azide–alkyne cycloaddition reaction to form triazolyl-polyglycines, at room temperature. The crisscrossed arrangement of monomers in adjacent layers ensured the formation of cross-laminated polymers.
Copper(I)-Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β-Tetrapeptide Analogues
Chen, Chun-Chi,Wang, Sheng-Fu,Su, Yung-Yu,Lin, Yuya A.,Lin, Po-Chiao
, p. 1326 - 1337 (2017/06/23)
A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α3β-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α3β-tetrapeptide framework have been successfully synthesized.
