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Expanding The Scope of Terminal Alkynes in Chemical Biology
Maza, Johnathan Charles
Maza, Johnathan Charles
Abstract
The terminal alkyne is one of the most widely used chemical moieties in chemical biology. Thanks to the relative absence of this functional group in biology, it has become a widespread functional handle for a plethora of biorthogonal chemistries. Our group has extended the scope of this functionality by developing a biological variant of the Glaser-Hay coupling, which brings together two terminal alkynes to form a diyne linkage. However, our initial findings revealed that the chemistry is plagued by protein degradation due to a deleterious copper(II) hydroxyl intermediate. Herein we extend the scope of the terimanl alkyne be developing a biological variant of the Cadiot-Chodkiewicz coupling, which brings together a bromoalkyne and a terminal alkyne to form a diyne linkage. Unlike the Glaser-Hay, the Cadiot-Chodkiewicz is thought to be net redox neutral. We found that this chemistry is biologically compatible and does indeed reduce copper(II)-mediated cytotoxicity while increasing rates of diyne formation. Finally, we extend our findings on diyne-forming chemistries by applying this conjugation to a variety of projects, ranging from undergraduate teaching labs, bioconjugate preparation, and protein function, thereby expanding the scope of this conjugation strategy.
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2016-01-01
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Chemistry
DOI
http://doi.org/10.21220/S28C70