Date of Award

2008

Publication Type

Master Thesis

Degree Name

M.Sc.

Department

Chemistry and Biochemistry

First Advisor

Siyaram Pandey

Keywords

Pure sciences; Biological sciences

Rights

info:eu-repo/semantics/openAccess

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Abstract

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.

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