17694-98-3Relevant articles and documents
LAT1 activity of carboxylic acid bioisosteres: Evaluation of hydroxamic acids as substrates
Zur, Arik A.,Chien, Huan-Chieh,Augustyn, Evan,Flint, Andrew,Heeren, Nathan,Finke, Karissa,Hernandez, Christopher,Hansen, Logan,Miller, Sydney,Lin, Lawrence,Giacomini, Kathleen M.,Colas, Claire,Schlessinger, Avner,Thomas, Allen A.
supporting information, p. 5000 - 5006 (2016/10/05)
Large neutral amino acid transporter 1 (LAT1) is a solute carrier protein located primarily in the blood–brain barrier (BBB) that offers the potential to deliver drugs to the brain. It is also up-regulated in cancer cells, as part of a tumor's increased metabolic demands. Previously, amino acid prodrugs have been shown to be transported by LAT1. Carboxylic acid bioisosteres may afford prodrugs with an altered physicochemical and pharmacokinetic profile than those derived from natural amino acids, allowing for higher brain or tumor levels of drug and/or lower toxicity. The effect of replacing phenylalanine's carboxylic acid with a tetrazole, acylsulfonamide and hydroxamic acid (HA) bioisostere was examined. Compounds were tested for their ability to be LAT1 substrates using both cis-inhibition and trans-stimulation cell assays. As HA-Phe demonstrated weak substrate activity, its structure–activity relationship (SAR) was further explored by synthesis and testing of HA derivatives of other LAT1 amino acid substrates (i.e., Tyr, Leu, Ile, and Met). The potential for a false positive in the trans-stimulation assay caused by parent amino acid was evaluated by conducting compound stability experiments for both HA-Leu and the corresponding methyl ester derivative. We concluded that HA's are transported by LAT1. In addition, our results lend support to a recent account that amino acid esters are LAT1 substrates, and that hydrogen bonding may be as important as charge for interaction with the transporter binding site.
Hydration of amino acids from ultrasonic measurements
Burakowski, Andrzej,Gliński, Jacek
experimental part, p. 12157 - 12161 (2011/01/11)
In this paper the results of compressibility of aqueous solutions of amino acids in water and in aqueous HCl and NaOH solutions at 25 °C are presented. The effect of the charged protonated amino groups and deprotonated carboxylic groups on the hydration number was tested. The idea of additivity of the hydration number with the constituents of the solute molecule was successfully applied and discussed.
Novel cyclopeptide and unique flavone from Desmos rostrata. Total synthesis of desmorostratone
Nguyen, Ngoc Tuan,Pham, Van Cuong,Litaudon, Marc,Guéritte, Fran?oise,Bodo, Bernard,Nguyen, Van Tuyen,Nguyen, Van Hung
experimental part, p. 7171 - 7176 (2009/12/24)
Two new compounds, a cyclic peptide desmocyclopeptide (1) and a special flavone desmorostratone (2) were isolated from the stem bark of Desmos rostrata, along with two known compounds, desmosdumotins B (3) and C (4). Their structures were established on the basis of the spectral data, including mass spectrometry and 2D NMR. The total synthesis of desmorostratone (2) was performed in order to confirm its structure as well as that of desmosdumotin C (4), which was a tautomeric mixture in the solution. Finally, cytotoxity of these compounds were evaluated. Desmosdumotin C (4) displayed a moderate inhibition activity against KB cell line with an IC50 of 19.2 μM, whereas the other products showed a weak inhibition against the same cell line target.
