BackIn recent years, rapid scientific advances in human genomics and proteomics have brought about the identification of new therapeutic targets (proteins of interest). Additionally, the development of high-throughput synthesis techniques has generated thousands of new chemical entities with potential therapeutic effect. “Therefore, analysing and screening these generated compounds in order to identify potential drug candidates presents a considerable challenge,” said Kaia-Liisa Habicht (PhD) who recently defended her doctoral thesis[1] at Tallinn University.
An Important Tool
In her thesis, she utilized bioaffinity chromatography to establish novel approaches for identifying potential drug candidates for several important therapeutic targets, including Adenosine triphosphate-binding cassette transporters (ABC transporters), such as Pgp, MRP1 and BCRP.
Habicht explained that ABC transporters are the key components in developing multidrug resistance, and thus are mainly responsible for failure of several cancer therapies. “Attenuation of ABC transporters using specific therapeutic agents is considered to be a potential option for establishing successful chemotherapy. By utilizing our high throughput screening approach, potential drug candidates that bind and/or inhibit these ABC transporters can be identified, thus leading to discovery of novel anticancer therapeutic agents,” she said.
The established approaches were utilized for studying interactions between pharmacologically important transmembrane proteins and biomolecules (e.g. drugs). Furthermore, the thesis demonstrated that established bioaffinity chromatography approaches could be exploited for high throughput screening and identification of novel drug molecules—thus being an important tool in the drug development process. “Bioaffinity chromatography is one of the key approaches that can be exploited for establishing drug screening and identification approaches for various important therapeutic targets,” Habicht added.
Opens Up New Possibilities
Habicht studied cell membrane models and gained a significant understanding of biomembrane compositions and their pharmacological importance as therapeutic targets during her Master’s program. In her PhD thesis she was more specific and deals with particular components of the membrane—proteins. The research was part of a collaboration between Tallinn University and Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (USA), which was initiated by her supervisor, professor Ruth Shimmo.
Previously, the method of bioaffinity chromatography has been used to study transmembrane proteins from only cellular membranes; within Habicht’s PhD work, it was expanded to nuclear and mitochondrial membranes. “These membranes contain important pharmacological targets too, so being able to study those proteins using this approach is essential,” Habicht noted. Furthermore, in addition to using cultivated cells, tissue samples were successfully used as a source of proteins of interest. According to Habicht, this opens up a possibility to compare and find differences between healthy and diseased individuals.
In the future, she would like to study screening for possible bioactive compounds from different plant extracts or compound libraries.
[1] Kaia-Liisa Habicht’s doctoral thesis Development of Bioaffinity Chromatography Columns for Studying Transmembrane Proteins of Different Biological Membranes is accessible at the ETERA site: http://www.etera.ee/zoom/30635/view?page=1&p=separate&view=0,0,2067,2834
This article was funded by the European Regional Development Fund through Estonian Research Council.
