Glucagon-like peptide 1 receptor (GLP-1R) is of interest in studying the body’s insulin pathways. To more clearly understand the active site of GLP-1R, strongly-binding compounds can be covalently attached through photoaffinity labeling. The bond from the ligand to the nearest amino acid residue in the active site acts as a tag that can give spatial constraints on the binding site. In 1996, Taniguchi et al. developed the molecule T-0632 (see Figure 1 below) to explore the cholecystokinin receptor, and found that it also binds to GLP-1R. Tibaduiza et al. were able to isolate the region of GLP-1R that binds T-0632. My research involves making photolabile isoquinoline derivatives that can be incorporated into T-0632. The derivatization begins with mono-iodinating 3-methylisoquinoline, then oxidizing the methyl group to a carboxylic acid, and finally incorporating the modified isoquinoline into a T-0632 analog. The iodide is then converted into a photolabile azide group that can be used to explore the active site of GLP-1R.

Synthesis of photolabile T-0632 derivatives to aid GLP-1R active site exploration

253rd National Meeting (2017)

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