Fragment-Based Ligand Discovery Using Protein-Observed 19F NMR: A Second Semester Organic Chemistry CURE Project

• Scott K. Bur ^[1] ; William C. K. Pomerantz ^[2] ; Morgan L. Bade ^[1] ; Clifford T. Gee ^[2]
  1. [1] Gustavus Adolphus College

     Gustavus Adolphus College

     City of Saint Peter, Estados Unidos

     
  2. [2] University of Minnesota

     University of Minnesota

     City of Minneapolis, Estados Unidos

     
• Localización: Journal of chemical education, ISSN 0021-9584, Vol. 98, Nº 6, 2021, págs. 1963-1973
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Curriculum-based undergraduate research experiences (CUREs) have been shown to increase student retention in STEM fields and are starting to become more widely adopted in chemistry curricula. Here we describe a 10-week CURE that is suitable for a second-semester organic chemistry laboratory course. Students synthesize small molecules and use protein-observed 19F (PrOF) NMR to assess the small molecule’s binding affinity to a target protein. The research project introduced students to multistep organic synthesis, structure–activity relationship studies, quantitative biophysical measurements (measuring Kd from PrOF NMR experiments), and scientific literacy. Docking experiments could be added to help students understand how changes in a ligand structure may affect binding to a protein. Assessment using the CURE survey indicates self-perceived skill gains from the course that exceed gains measured in a traditional and an inquiry-based laboratory experience. Given the speed of the binding experiment and the alignment of the synthetic methods with a second-semester organic chemistry laboratory course, a PrOF NMR fragment-based ligand discovery lab can be readily implemented in the undergraduate chemistry curriculum.