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