In 2018,Chien, Huan-Chieh; Colas, Claire; Finke, Karissa; Springer, Seth; Stoner, Laura; Zur, Arik A.; Venteicher, Brooklynn; Campbell, Jerome; Hall, Colton; Flint, Andrew; Augustyn, Evan; Hernandez, Christopher; Heeren, Nathan; Hansen, Logan; Anthony, Abby; Bauer, Justine; Fotiadis, Dimitrios; Schlessinger, Avner; Giacomini, Kathleen M.; Thomas, Allen A. published 《Reevaluating the substrate specificity of the L-type amino acid transporter (LAT1)》.Journal of Medicinal Chemistry published the findings.Electric Literature of C11H24N2O The information in the text is summarized as follows:
The L-type amino acid transporter 1 (LAT1, SLC7A5) transports essential amino acids across the blood-brain barrier (BBB) and into cancer cells. To utilize LAT1 for drug delivery, potent amino acid promoieties are desired, as prodrugs must compete with millimolar concentrations of endogenous amino acids. To better understand ligand-transporter interactions that could improve potency, we developed structural LAT1 models to guide the design of substituted analogs of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogs were tested in cis-inhibition and trans-stimulation cell assays to determine potency and uptake rate. Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents. Addnl., the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Our findings have broad implications to the development of new treatments for brain disorders and cancer. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8Electric Literature of C11H24N2O)
tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.Electric Literature of C11H24N2O
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics