Structural determination of novel ligands in complex with galectin-8N and galectin-3C, and the discovery of new leads through fragment screening
(2024) KEMR10 20232Department of Chemistry
- Abstract (Swedish)
- This thesis aimed to explore the binding pocket of galectin-8N and galectin-3C. Both structure-based drug design and fragment-based drug discovery were utilized in this project, exemplifying the benefits of the different approaches. Structural determination of the proteins in complex with both high affinity ligands, and small fragments was achieved through x-ray crystallography. The structures of complexes of three novel ligands with galectin-8N and of two novel ligands in complex with galectin-3C are here presented, along with structures of three fragments in complex with galectin-8N. Two of the fragments bind to non-conserved amino acids in a hydrophobic pocket of galectin-8N. Furthering the understanding of this pocket is important for... (More)
- This thesis aimed to explore the binding pocket of galectin-8N and galectin-3C. Both structure-based drug design and fragment-based drug discovery were utilized in this project, exemplifying the benefits of the different approaches. Structural determination of the proteins in complex with both high affinity ligands, and small fragments was achieved through x-ray crystallography. The structures of complexes of three novel ligands with galectin-8N and of two novel ligands in complex with galectin-3C are here presented, along with structures of three fragments in complex with galectin-8N. Two of the fragments bind to non-conserved amino acids in a hydrophobic pocket of galectin-8N. Furthering the understanding of this pocket is important for the development of high selectivity inhibitors. The third fragment displayed binding interactions mimicking those of carbohydrates in complex with galectin-8N. These interactions are universal for the galectin family and the structure presented in this thesis is the first of a non-carbohydrate bound to galectin-8N in this way. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9149760
- author
- Ahl, Erica LU
- supervisor
-
- Derek Logan LU
- organization
- course
- KEMR10 20232
- year
- 2024
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Biochemistry, galectin-8, galectin-3, x-ray crystallography
- language
- English
- id
- 9149760
- date added to LUP
- 2024-03-20 12:51:56
- date last changed
- 2024-03-20 12:51:56
@misc{9149760, abstract = {{This thesis aimed to explore the binding pocket of galectin-8N and galectin-3C. Both structure-based drug design and fragment-based drug discovery were utilized in this project, exemplifying the benefits of the different approaches. Structural determination of the proteins in complex with both high affinity ligands, and small fragments was achieved through x-ray crystallography. The structures of complexes of three novel ligands with galectin-8N and of two novel ligands in complex with galectin-3C are here presented, along with structures of three fragments in complex with galectin-8N. Two of the fragments bind to non-conserved amino acids in a hydrophobic pocket of galectin-8N. Furthering the understanding of this pocket is important for the development of high selectivity inhibitors. The third fragment displayed binding interactions mimicking those of carbohydrates in complex with galectin-8N. These interactions are universal for the galectin family and the structure presented in this thesis is the first of a non-carbohydrate bound to galectin-8N in this way.}}, author = {{Ahl, Erica}}, language = {{eng}}, note = {{Student Paper}}, title = {{Structural determination of novel ligands in complex with galectin-8N and galectin-3C, and the discovery of new leads through fragment screening}}, year = {{2024}}, }