Date of Award
Chemistry and Biochemistry
Pure sciences; Biological sciences
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Oxidative-stress-induced neuronal apoptosis has been implicated in the development of neurodegenerative diseases such as ischemic stroke. Pro-apoptotic proteins including Caspase 3 and Bax are critical components of the apoptotic pathway. In this study we aimed to identify specific inhibitors of Caspase 3 and Bax. We isolated two single domain antibodies (sdAbs) against Caspase 3; one (VhhCasp3 1) capable of blocking Caspase 3 function in vitro and in vivo, and the other (VhhCasp32) acting oppositely. The genes and antibodies coded by them can be used as a platform for therapeutic development for neuroprotective or anti-cancer agents.
We also screened a pharmacaphore library of small molecular weight compounds capable of binding to Bax and blocking function in the same manner as a specific anti-Bax sdAb inhibitor previously found by our group. We found "compound 22," which was capable of competitive binding to Bax and blocked Bax function in vitro and in vivo.
McGonigal, Katrina, "Identification and functional characterization of modulators of pro-apoptotic proteins Caspase 3 and Bax" (2008). Electronic Theses and Dissertations. 8078.