@article{dcd857e8b47b4ababe7787c67d2ac900,
title = "L-Type amino acid transporter 1 activity of 1,2,3-triazolyl analogs of L-histidine and L-tryptophan",
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.",
keywords = "Amino acid, Blood-brain barrier, Cancer, Click chemistry, Membrane transporter, Solute carrier family, Triazole",
author = "Colton Hall and Hannah Wolfe and Alyssa Wells and Chien, {Huan Chieh} and Claire Colas and A. Schlessinger and Giacomini, {Kathleen M.} and Thomas, {Allen A.}",
note = "Funding Information: This work was supported by the National Institutes of Health's National Institute of Neurological Disorders and Stroke Grant R15 NS099981 (to A.A.T), the National Institutes of Health's National Institute of General Medical Sciences Grant R01 GM117163 (to H.C.C. and K.M.G.) and R01 GM108911 (to A.S. and C.C.). We appreciate OpenEye Scientific Software Inc. for granting us access to its high-performance molecular modeling applications through its academic license program. Funding Information: This work was supported by the National Institutes of Health {\textquoteright}s National Institute of Neurological Disorders and Stroke Grant R15 NS099981 (to A.A.T), the National Institutes of Health 's National Institute of General Medical Sciences Grant R01 GM117163 (to H.C.C. and K.M.G.) and R01 GM108911 (to A.S. and C.C.). We appreciate OpenEye Scientific Software Inc. for granting us access to its high-performance molecular modeling applications through its academic license program. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = aug,
day = "15",
doi = "10.1016/j.bmcl.2019.06.033",
language = "English (US)",
volume = "29",
pages = "2254--2258",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "16",
}