95260-60-9Relevant articles and documents
Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1)
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.
supporting information, p. 7358 - 7373 (2018/08/06)
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 analogues of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogues 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. Additionally, 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 formation of a crystalline oxazolidin-5-one from (L)-alanine and its use as a chiral template in the practical synthesis of α-substituted alanine esters
Eriksson, Magnus,Napolitano, Elio,Xu, Jinghua,Kapadia, Suresh,Byrne, Denis,Nummy, Laurence,Grinberg, Nelu,Shen, Sherri,Lee, Heewon,Farina, Vittorio
, p. 566 - 573 (2007/10/03)
Three different protocols to synthesize oxazolidin-5-ones have been studied with the goal to develop a method to synthesize a diastereomerically pure oxazolidin-5-one. A novel method is reported that uses a dynamic crystallization-induced asymmetric transformation to isolate a single diastereomer of an oxazolidin-5-one in 92% yield on kilogram scale. Alkylation of the oxazolidin-5-one template leads to good-to-excellent yields of N-protected α-substituted alanine esters in >98-99% ee. Schweizerische Chemische Gesellschaft.
Synthesis of Phenylalanine-based Cyclic Acylated Enamino Ester Dipeptide Analogues: Inhibitors of α-Chymotrypsin. X-Ray Molecular Structure of (2'S,4'R)-4'-Benzyl-3'-benzyloxycarbonyl-5'-oxo-2'-phenyloxazolidin-4'-ylacetic Acid
Abell, Andrew D.,Oldham, Mark D.,Taylor, Jane M.
, p. 953 - 962 (2007/10/02)
Alkylation of the (S)-phenylalanine-derived syn-oxazolidinone 8 with BrCH2CO2CHPh2 gave compound 9, a key precursor to the β-keto ester 11 and the keto acid phosphorane 17.Compound 17 gave the enolactone 24 on heating and the bromo enolactone 19 and 20 on
