95260-60-9Relevant 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.
A novel peptide stapling strategy enables the retention of ring-closing amino acid side chains for the Wnt/β-catenin signalling pathway
Wu, Ye,Li, Ye-Hua,Li, Xiang,Zou, Yan,Liao, Hong-Li,Liu, Lei,Chen, Ye-Guang,Bierer, Donald,Hu, Hong-Gang
, p. 7368 - 7373 (2017/10/30)
The all-hydrocarbon peptide stapling strategy has recently been extensively explored in drug discovery. There remains the potential for improvement regarding the retention of the amino acid side chains at the stapled positions. Herein, we describe a new s
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 and dopamine receptor modulating activity of substituted bicyclic thiazolidine lactam peptidomimetics of L-prolyl-L-leucyl-glycinamide
Khalil, Ehab M.,Pradhan, Ashish,Ojala, William H.,Gleason, William B.,Mishra, Ram K.,Johnson, Rodney L.
, p. 2977 - 2987 (2007/10/03)
6-Substituted bicyclic thiazolidine lactam peptidomimetics of Pro-Leu- Gly-NH2 (1) were synthesized to test the hypothesis that incorporation of a hydrophobic side chain into the bicyclic thiazolidine lactam scaffold would further enhance the d
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
Design and Synthesis of a Conformationally Restricted Cysteine Protease Inhibitor
Cheng, Hengmiao,Keitz, Paul,Jones, J. Bryan
, p. 7671 - 7676 (2007/10/02)
Using the X-ray analyses of papain and papain-chloromethyl ketone inhibitor complexes as representative cysteine protease structures, molecular graphics analyses were applied to design (4R,1'S)-2-ethyl>-4-benzyl-4-(2-oxoeth
HETEROCYCLIC PEPTIDE RENIN INHIBITORS
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, (2008/06/13)
A renin inhibiting compound of the formula STR1 wherein X is N, O or CH; R 1 is absent or a functional group; A and L are independently selected from absent, C=O, SO 2 and CH 2 ; D is C=O, SO. sub.2 or CH 2 ; Y is N or CH; R 2 is hydrogen, loweralkyl or substituted alkyl; Z is a functional group; R 3 is loweralkyl or substituted alkyl; n is 0 or 1; and T is a mimic of the Leu-Val cleavage site of angiotensinogen; or a pharmaceutically acceptable salt, ester or prodrug thereof.
ENANTIORETENTIVE ALKYLATION OF ACYCLIC AMINO ACIDS
Karady, Sandor,Amato, Joseph S.,Weinstock, Leonard M.
, p. 4337 - 4340 (2007/10/02)
A stereospecific method is described for the alkylation of acyclic amino acids (alanine and phenylalanine) which proceeds with retention of configuration.The method involves a) conversion of the amino acid to the predominantly cis 2-aryl-3-carbobenzyloxy oxazolidinones (2 and 8), b) alkylation of the potassium enolate with CH3I or PhCH2Br, c) base hydrolysis and hydrogenolysis to afford the alkylated amino acid.
