Thesis supervisor: Ádám Golcs
Location of studies (in Hungarian): BME Department of Organic Chemistry and Technology Abbreviation of location of studies: BME
Description of the research topic:
Nowadays, the need for high throughput is raising in the field of synthetic chemistry. Numerous innovations are emerging from the side of parallel synthesis methods and automation. However, the development of synthesis-supporting separation techniques is still tied to the transformation of traditional instrumental analytical techniques (e.g., HPLC, SFC, CE and their miniaturized parallel or lab-on-a-chip implementations) that are difficult to optimize for high throughput [1]. Since targeted subpreparative-scale (i.e., micro- and nanomolar) automated high-throughput experimentations are typically based on microtiter plate platforms integrated with robotic liquid handling equipment, it would be obvious to replace these synthesis-supporting separation techniques with integrable microtiter plate-based devices.
The research project includes the preparation of the new artificial receptors, their characterization, post-synthetic modifications and also the utilization of their molecular recognition ability for device development.
Development of the novel supramolecular devices will be carried out by physically or covalently attaching potential host molecules to preactivated (surface treated or linker-functionalized) polymer surfaces or via incorporation into microplate-integrable membranes. Molecular recognition would be exploited in both membrane-integrated “sandwich plates” and surface-modified single-assay systems, while concentration gradient, external pressure, electronic effects or even their combinations with a selective facilitation or retardment would be optimized as driving forces of material transport.
Replacing conventional methods by the proposed devices in high-throughput purifications will enable the favorable direct plate-to-plate material transfer, while overcoming the limitations of straight-to-analysis assays. This would result in a reduced number of false positive and negative outputs during first-pass screenings of new compounds to reduce the overall risk in early-stage drug-discovery projects.
[1] Jones, M., Goodyear, R. L. (2023). High-Throughput Purification in Drug Discovery: Scaling New Heights of Productivity. ACS Medicinal Chemistry Letters, 14(7), 916-919. DOI: 10.1021/acsmedchemlett.3c00073
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