473259-95-9Relevant academic research and scientific papers
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.
Cyclic Peptides Incorporating Phosphotyrosine Mimetics as Potent and Specific Inhibitors of the Grb7 Breast Cancer Target
Watson, Gabrielle M.,Gunzburg, Menachem J.,Ambaye, Nigus D.,Lucas, William A. H.,Traore, Daouda A.,Kulkarni, Ketav,Cergol, Katie M.,Payne, Richard J.,Panjikar, Santosh,Pero, Stephanie C.,Perlmutter, Patrick,Wilce, Matthew C. J.,Wilce, Jacqueline A.
, p. 7707 - 7718 (2015/10/20)
The Grb7 adaptor protein is a therapeutic target for both TNBC and HER2+ breast cancer. A nonphosphorylated cyclic peptide 1 (known as G7-18NATE) inhibits Grb7 via targeting the Grb7-SH2 domain, but requires the presence of phosphate ions for both affinit
Type b botulism toxin inhibitors
-
Page 9, (2010/02/08)
The invention relates to novel compounds of genera formula (I), with inhibitory properties for the type B botulism toxin activity, the methods for preparation thereof and corresponding pharmaceutical compositions. The invention further relates to correspo
Stereospecific synthesis of 4-carboxyphenylalanine and derivatives for use in Fmoc-based solid-phase peptide synthesis
Wang, Wei,Obeyesekere, Nihal U.,McMurray, John S.
, p. 6661 - 6664 (2007/10/03)
Starting from N(α)-benzyloxycarbonyl-L-tyrosine(O-triflate) benzyl ester, we have prepared enantiomerically pure 4-carboxyphenylalanine and 4-methoxycarbonylphenylalanine derivatives using palladium (0) catalyzed carbonylation reactions. These unnatural amino acids were suitably protected and were used in solid-phase peptide synthesis using the Fmoc/t-butyl approach.
