Development of a methodology for testing the interaction of proteins modified with biologically active compounds with their receptors
The subject of the project is to develop a research methodology for protein-receptor systemsbased on experimental techniques available at both institutions. The preparation of biosensorsenabling immobilization of proteins with histidine tags used for measuring receptor-proteininteraction using QCM or SPR techniques, will be a particular challenge. These tests will becarried out for the modified transferrin-transferrin receptor system. Ruthenium complexes thatare in Phase I or II of clinical trials as antitumor compounds have been selected as proteinmodifiers. One of the critical aspects of drug distribution in the body is the way it istransported inside the cells constituting its molecular target in the body. Regard tometallopharmaceuticals derived from ruthenium complexes, several possible mechanismsexplaining this process is suggested, including active transport involving transferrin (Tf) andtransferrin receptors (TfR). So far this hypothesis has never been verified. Determining theconditions for effective interaction of the ruthenium-modified transferrin compounds with thetransferrin receptor would allow proposing new drug delivery protocols to increase theirtransport into the cell.
The measurable result of the research will be i) verification of the current state of knowledgeon the recognition of Ru-transferrin adducts by the transferrin receptor, ii) proposing aresearch methodology for transferrin modified with other compounds, and iii) other protein-receptor systems.
Innovation: so far, no literature reports have been published regarding the use of QCM or SPRtechniques to study the transferrin interaction with the transferrin receptor, only a few studieson the protein-receptor interaction for other systems are known.
