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

Scott K. Bur, William C.K. Pomerantz, Morgan L. Bade, Clifford T. Gee

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1963-1973
Number of pages11
JournalJournal of Chemical Education
Volume98
Issue number6
DOIs
StatePublished - May 11 2021

Bibliographical note

Funding Information:
This work was supported by a Cottrell Scholar award, a program of Research Corporation for Science Advancement. S.K.B. acknowledges National Science Foundation Grant RUI1806228, and S.K.B. and W.C.K.P. acknowledge a National Science Foundation Research Opportunity Award associated with Grant CHE1352091. We thank Dr. Laura Hawk for providing a sample of Ni-DTPA and Dr. Jorden Johnson for assistance with PrOF NMR during the development of the project. We also thank Dr. Jane Wissinger for assistance with gathering data for the U of MN CURE survey.

Publisher Copyright:
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Keywords

  • Inquiry-Based/Discovery Learning
  • Laboratory Instruction
  • NMR Spectroscopy
  • Organic Chemistry
  • Proteins/Peptides

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