Master of Science (M.Sc.)
Douglas D Young
Lisa M Landino
William R McNamara
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.
© The Author
Maza, Johnathan Charles, "Expanding The Scope of Terminal Alkynes in Chemical Biology" (2016). Dissertations, Theses, and Masters Projects. Paper 1477068470.
Available for download on Friday, September 27, 2019