l-Type amino acid transporter 1 activity of 1,2,3-triazolyl analogs of l-histidine and l-tryptophan
- Author(s)
- Colton Hall, Hannah Wolfe, Alyssa Wells, Huan-Chieh Chien, Claire Colas, Avner Schlessinger, Kathleen M Giacomini, Allen A Thomas
- Abstract
A series of 1,2,3-triazole analogs of the amino acids l-histidine and l-tryptophan were modeled, synthesized and tested for l-type amino acid transporter 1 (LAT1; SLC7A5) activity to guide the design of amino acid-drug conjugates (prodrugs). These triazoles were conveniently prepared by the highly convergent Huisgen 1,3-dipolar cycloaddition (Click Chemistry). Despite comparable predicted binding modes, triazoles generally demonstrated reduced cell uptake and LAT1 binding potency relative to their natural amino acid counterparts. The structure-activity relationship (SAR) data for these triazoles has important ramifications for treating cancer and brain disorders using amino acid prodrugs or LAT1 inhibitors.
- Organisation(s)
- Department of Pharmaceutical Chemistry
- External organisation(s)
- University of Nebraska - Kearney, University of California, San Francisco, Icahn School of Medicine at Mount Sinai, New York
- Journal
- Bioorganic & Medicinal Chemistry Letters
- Volume
- 29
- Pages
- 2254-2258
- No. of pages
- 5
- ISSN
- 0960-894X
- DOI
- https://doi.org/10.1016/j.bmcl.2019.06.033
- Publication date
- 08-2019
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- Computer aided design (CAD)
- Portal url
- https://ucris.univie.ac.at/portal/en/publications/ltype-amino-acid-transporter-1-activity-of-123triazolyl-analogs-of-lhistidine-and-ltryptophan(7f69a562-6195-467b-b3c8-124a9ab4bab0).html