L-Type amino acid transporter 1 activity of 1,2,3-triazolyl analogs of L-histidine and L-tryptophan

Colton Hall, Hannah Wolfe, Alyssa Wells, Huan Chieh Chien, Claire Colas, A. Schlessinger, Kathleen M. Giacomini, Allen A. Thomas

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2254-2258
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number16
StatePublished - Aug 15 2019


  • Amino acid
  • Blood-brain barrier
  • Cancer
  • Click chemistry
  • Membrane transporter
  • Solute carrier family
  • Triazole

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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