Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6
Malaria is a potentially life-threatening disease caused by Plasmodium parasites. While existing drugs have been effective, the emergence of drug resistance necessitates the identification of new drug targets and the development of potential drugs. Plasmodium falciparum Protein Kinase 6 (PfPK6) has...
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| Format: | Final Year Project (FYP) |
| Language: | English |
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Nanyang Technological University
2023
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| Online Access: | https://hdl.handle.net/10356/171865 |
| _version_ | 1811694734020706304 |
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| author | Yew, Wei Ni |
| author2 | Julien Lescar |
| author_facet | Julien Lescar Yew, Wei Ni |
| author_sort | Yew, Wei Ni |
| collection | NTU |
| description | Malaria is a potentially life-threatening disease caused by Plasmodium parasites. While existing drugs have been effective, the emergence of drug resistance necessitates the identification of new drug targets and the development of potential drugs. Plasmodium falciparum Protein Kinase 6 (PfPK6) has been genetically identified as a promising new target crucial for the survival of Plasmodium falciparum. This study aimed to validate the binding of Compound 1 to purified PfPK6, assess the potential inhibitory effects of Compound 1 on PfPK6, and explore its mechanism of action within the PfPK6 binding site. Through differential scanning fluorimetry (DSF) and isothermal titration calorimetry (ITC), it was confirmed that Compound 1 binds to PfPK6 with moderate affinity. Additionally, enzymatic assay provided evidence of Compound 1 inhibiting PfPK6 activity. Despite numerous attempts, the atomic interaction between Compound 1 and PfPK6 has yet to unravel due to challenges in co-crystallizing PfPK6 with Compound 1 and crystallizing PfPK6 itself. Nonetheless, this study has demonstrated the ability of Compound 1 to bind to and inhibit PfPK6, shedding light on its potential as a therapeutic target for combating malaria. |
| first_indexed | 2024-10-01T07:12:16Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/171865 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:12:16Z |
| publishDate | 2023 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1718652023-11-21T06:56:58Z Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6 Yew, Wei Ni Julien Lescar School of Biological Sciences NTU Institute of Structural Biology Julien@ntu.edu.sg Science::Biological sciences Malaria is a potentially life-threatening disease caused by Plasmodium parasites. While existing drugs have been effective, the emergence of drug resistance necessitates the identification of new drug targets and the development of potential drugs. Plasmodium falciparum Protein Kinase 6 (PfPK6) has been genetically identified as a promising new target crucial for the survival of Plasmodium falciparum. This study aimed to validate the binding of Compound 1 to purified PfPK6, assess the potential inhibitory effects of Compound 1 on PfPK6, and explore its mechanism of action within the PfPK6 binding site. Through differential scanning fluorimetry (DSF) and isothermal titration calorimetry (ITC), it was confirmed that Compound 1 binds to PfPK6 with moderate affinity. Additionally, enzymatic assay provided evidence of Compound 1 inhibiting PfPK6 activity. Despite numerous attempts, the atomic interaction between Compound 1 and PfPK6 has yet to unravel due to challenges in co-crystallizing PfPK6 with Compound 1 and crystallizing PfPK6 itself. Nonetheless, this study has demonstrated the ability of Compound 1 to bind to and inhibit PfPK6, shedding light on its potential as a therapeutic target for combating malaria. Bachelor of Science in Biological Sciences 2023-11-14T06:58:59Z 2023-11-14T06:58:59Z 2023 Final Year Project (FYP) Yew, W. N. (2023). Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6. Final Year Project (FYP), Nanyang Technological University, Singapore. https://hdl.handle.net/10356/171865 https://hdl.handle.net/10356/171865 en application/pdf Nanyang Technological University |
| spellingShingle | Science::Biological sciences Yew, Wei Ni Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6 |
| title | Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6 |
| title_full | Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6 |
| title_fullStr | Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6 |
| title_full_unstemmed | Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6 |
| title_short | Unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6 |
| title_sort | unravelling structure activity relationship between an antimalarial compound and plasmodium falciparum protein kinase 6 |
| topic | Science::Biological sciences |
| url | https://hdl.handle.net/10356/171865 |
| work_keys_str_mv | AT yewweini unravellingstructureactivityrelationshipbetweenanantimalarialcompoundandplasmodiumfalciparumproteinkinase6 |