4277-34-3Relevant articles and documents
General, Divergent Platform for Diastereoselective Synthesis of trans-Cyclooctenes with High Reactivity and Favorable Physiochemical Properties**
Pigga, Jessica E.,Rosenberger, Julia E.,Jemas, Andrew,Boyd, Samantha J.,Dmitrenko, Olga,Xie, Yixin,Fox, Joseph M.
supporting information, p. 14975 - 14980 (2021/05/31)
trans-Cyclooctenes (TCOs) are essential partners in the fastest known bioorthogonal reactions, but current synthetic methods are limited by poor diastereoselectivity. Especially hard to access are hydrophilic TCOs with favorable physicochemical properties for live cell or in vivo experiments. Described is a new class of TCOs, “a-TCOs”, prepared in high yield by stereocontrolled 1,2-additions of nucleophiles to trans-cyclooct-4-enone, which itself was prepared on a large scale in two steps from 1,5-cyclooctadiene. Computational transition-state models rationalize the diastereoselectivity of 1,2-additions to deliver a-TCO products, which were also shown to be more reactive than standard TCOs and less hydrophobic than even a trans-oxocene analogue. Illustrating the favorable physicochemical properties of a-TCOs, a fluorescent TAMRA derivative in live HeLa cells was shown to be cell-permeable through intracellular Diels–Alder chemistry and to wash out more rapidly than other TCOs.
A Bioorthogonal Click Chemistry Toolbox for Targeted Synthesis of Branched and Well-Defined Protein–Protein Conjugates
Baalmann, Mathis,Bitsch, Sebastian,Deweid, Lukas,Ilkenhans, Nadja,Kolmar, Harald,Neises, Laura,Schneider, Hendrik,Werther, Philipp,Wilhelm, Jonas,Wolfring, Martin,Wombacher, Richard,Ziegler, Michael J.
, p. 12885 - 12893 (2020/06/02)
Bioorthogonal chemistry holds great potential to generate difficult-to-access protein–protein conjugate architectures. Current applications are hampered by challenging protein expression systems, slow conjugation chemistry, use of undesirable catalysts, or often do not result in quantitative product formation. Here we present a highly efficient technology for protein functionalization with commonly used bioorthogonal motifs for Diels–Alder cycloaddition with inverse electron demand (DAinv). With the aim of precisely generating branched protein chimeras, we systematically assessed the reactivity, stability and side product formation of various bioorthogonal chemistries directly at the protein level. We demonstrate the efficiency and versatility of our conjugation platform using different functional proteins and the therapeutic antibody trastuzumab. This technology enables fast and routine access to tailored and hitherto inaccessible protein chimeras useful for a variety of scientific disciplines. We expect our work to substantially enhance antibody applications such as immunodetection and protein toxin-based targeted cancer therapies.
COMPOSITIONS AND METHODS FOR DELIVERING A SUBSTANCE TO A BIOLOGICAL TARGET
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Paragraph 0106; 0107, (2020/03/26)
The present application provides compositions and methods using bioorthogonal inverse electron demand Diels-Alder cycloaddition reaction for rapid and specific covalent delivery of a payload to a ligand bound to a biological target.
