Applications of biophysical methods in small-molecule modulators targeting protein function


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The research of Wenjia Wang described in her thesis covers a combination of biophysical methods in investigating the small-molecule modulator targeting protein function. One of them, an important application mentioned in the structure-based drug design (SBDD). SBDD takes advantages of the knowledge and basic understanding of the 3D structure of biomolecules (from X-ray Crystallography, Cryo-EM or nuclear magnetic resonance) to design, potential binders (small-molecules, peptides, or Antibodies).

In her thesis, she started with a review on known artificial macrocycles 63O/P/Q targeting human IL17A. Based on the known structures, an amino acid derives scaffold was designed and screened by microscale thermophoresis (MST) and differential scanning fluorimetry(DSF). Furthermore, a novel small molecule series was discovered by a combination of X-ray Crystallography and MST rely on the previous experience. Additionally, she worked on solving other small-molecule modulators with target proteins including the structure of pyridoxal kinase from Plasmodium falciparum (Pf Pdxk) complex with AMP-PNP and PL and bovine Carbonic anhydrase II (bCAII) with ligand-directed diazo transfer probes. In all, her thesis described a story in how multiple biophysical methods contributed to small-molecule modulators research, especially in structure-based drug design.
Originele taal-2English
KwalificatieDoctor of Philosophy
Toekennende instantie
  • Rijksuniversiteit Groningen
  • Dömling, Alex, Supervisor
  • Groves, Matthew, Supervisor
  • van Dijl, Jan Maarten, Beoordelingscommissie
  • Holak, Tad A., Beoordelingscommissie, Externe Persoon
  • Slotboom, Dirk, Beoordelingscommissie
Datum van toekenning12-feb-2021
Plaats van publicatie[Groningen]
StatusPublished - 2021

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