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Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego PAN
Contributor:Misicka-Kęsik, Aleksandra (Promotor) ; Lipiński, Piotr F.J. (Promotor)
Publisher:Instytut Medycyny Doswiadczalnej i Klinicznej im. Miroslawa Mossakowskiego PAN
Place of publishing: Date issued/created: Degree name: Level of degree: Degree discipline : Degree grantor:Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego PAN
Type of object: Coordinate uncertainty in meters: Subject and Keywords:Neurokonin1 receptor ; NK1R antagonist ; Molecular docking ; Target-specific scoring functions
Abstract:
The neurokinin NK1 receptor (NK1R) along with its endogenous ligand, substance P, takes part in the regulation of many physiological and pathological processes, which renders the NK1R an important molecular target for therapies. Newer approaches to the application of NK1R as a therapeutic target require searching for new ligands of this receptor or appropriate modifications of the already existing compounds. The aim of this doctoral project was the design and synthesis of a library of novel phenylalanine and tryptophan derivatives as potential ligands of NK1R. A total of 94 compounds were obtained and subjected to biological evaluation. Data on the NK1R receptor affinity served for the analysis of the structure–activity relationships in the obtained libraries. Some of the obtained compounds were also tested in the study of influence on the cell viability. The investigated compunds were characterized by varied activity towards COLO679 cancer cells and normal BJ cells. The second goal of my project was the development of scoring functions specific for NK1R. In the first stage of my computational work, I found that the original scoring function of AutoDock Vina program has a relatively poor efficacy in evaluating the binding energies of NK1R ligands and distinguishing active and nonactive compounds. Next, the obtained experimental data on NK1R affinity of my newly synthesized compounds as well as the literature data were used to train scoring functions specific for NK1R. The new scoring turned out to be more effective in virtual screening compared to the original scoring function of the AutoDock Vina program.
IMDiK PAN, ZS 437 ; click here to follow the link
Language: Rights:Creative Commons Attribution BY 4.0 license
Terms of use:Copyright-protected material. [CC BY 4.0] May be used within the scope specified in Creative Commons Attribution BY 4.0 license, full text available at: ; -
Digitizing institution:Mossakowski Medical Research Institute PAS
Original in:Library of the Mossakowski Medical Research Institute PAS
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