Construction of the C15-C30 subunit of dolabelide utilizing a temporary phosphate tether is described. Two routes are reported that make use of the orthogonal protecting- and leaving-group properties innate to phosphate esters. One route relies on a selective terminal oxidation, while a second utilizes a CM/selective hydrogenation sequence. Both routes depend on a highly regio- and diastereoselective cuprate addition to set the requisite stereochemistry at C22.
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http://dx.doi.org/10.1021/ol8001865 | DOI Listing |
Proc Natl Acad Sci U S A
December 2024
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599.
Adaptor protein complex-3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 adopts a constitutively open conformation compared to the related AP-1 and AP-2 coat complexes, which are inactive until undergoing large conformational changes upon membrane recruitment. How AP-3 is regulated is therefore an open question.
View Article and Find Full Text PDFIn Silico Plants
August 2024
Department of Chemical and Biomolecular Engineering, University of Tennessee-Knoxville, Knoxville, TN 37996, USA.
Guard cell movements depend, in part, on the remodelling of vacuoles from a highly fragmented state to a fused morphology during stomata opening. Indeed, full opening of plant stomata requires vacuole fusion to occur. Fusion of vacuole membranes is a highly conserved process in eukaryotes, with key roles played by two multi-subunit complexes: HOPS (homotypic fusion and vacuolar protein sorting) and SNARE (soluble NSF attachment protein receptor).
View Article and Find Full Text PDFNat Commun
November 2024
Division of Neurosciences and Cellular Structure, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
ARL5 is a member of the ARF family of small GTPases that is recruited to the trans-Golgi network (TGN) by another ARF-family member, ARFRP1, in complex with the transmembrane protein SYS1. ARL5 recruits its effector, the multisubunit tethering complex GARP, to promote SNARE-dependent fusion of endosome-derived retrograde transport carriers with the TGN. To further investigate the function of ARL5, we sought to identify additional effectors.
View Article and Find Full Text PDFACS Synth Biol
December 2024
Structural Biology Initiative, CUNY Advanced Science Research Center, New York, New York 10031, United States.
J Vis Exp
October 2024
Department of Chemistry, University of Zurich;
Single-molecule Förster Resonance Energy Transfer (smFRET) excels in studying dynamic biomolecules by allowing precise observation of their conformational changes over time. To monitor RNA dynamics with smFRET, we developed a method to covalently label RNAs at their termini with a FRET pair of fluorophores. This direct end-labeling strategy targets the 5'-phosphate by carbodiimide (EDC)/N-hydroxysuccinimide (NHS) activation and the 3'-ribose by periodate oxidation, which can be adapted to other RNAs regardless of their size and sequence to study them independently of artificial modifications.
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