Nγ-Aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site

被引：132

作者：

Esslinger, CS ^{[1
]}

Cybulski, KA ^{[1
]}

Rhoderick, JF ^{[1
]}

机构：

[1] Univ Montana, NIH, COBRE, Ctr Ctruct & FUnct Neurosci,Dept Biomed & Pharmac, Missoula, MT 59812 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 04期

关键词：

pharmacophore; modeling; inhibition; H-bonding;

D O I：

10.1016/j.bmc.2004.11.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Analogues of L-glutamine were designed and synthesized to test a hydrogen-bond hypothesis between ligand and neutral amino acid transporter ASCT2. The key design feature contains a substituted phenyl ring on the amide nitrogen that contains electron withdrawing and electron donating groups that alter the pK(a) of the amide NH. Through this study a preliminary binding site map has been developed, and a potent commercially available competitive inhibitor of the ASCT2 transporter has been identified. (C) 2004 Elsevier Ltd. All rights reserved.

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页码：1111 / 1118

页数：8

相关论文

共 31 条

[1] Glutamine transport and human hepatocellular transformation [J].

Bode, BP ;

Souba, WW .

JOURNAL OF PARENTERAL AND ENTERAL NUTRITION, 1999, 23 (05) :S33-S37

[2] Recent molecular advances in mammalian glutamine transport [J].

Bode, BP .

JOURNAL OF NUTRITION, 2001, 131 (09) :2475S-2485S

[3] Glutamine alimentation in catabolic state [J].

Boelens, PG ;

Nijveldt, RJ ;

Houdijk, APJ ;

Meijer, S ;

van Leeuwen, PAM .

JOURNAL OF NUTRITION, 2001, 131 (09) :2569S-2577S

[4] Cell-specific expression of the glutamine transporter SN1 suggests differences in dependence on the glutamine cycle [J].

Boulland, JL ;

Osen, KK ;

Levy, LM ;

Danbolt, NC ;

Edwards, RH ;

Storm-Mathisen, J ;

Chaudhry, FA .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2002, 15 (10) :1615-1631

[5]

Bourke E, 1992, Contrib Nephrol, V100, P58

[6] CONFORMATIONALLY DEFINED NEUROTRANSMITTER ANALOGS - SELECTIVE-INHIBITION OF GLUTAMATE UPTAKE BY ONE PYRROLIDINE-2,4-DICARBOXYLATE DIASTEREOMER [J].

BRIDGES, RJ ;

STANLEY, MS ;

ANDERSON, MW ;

COTMAN, CW ;

CHAMBERLIN, AR .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (02) :717-725

[7]

Bröer A, 1999, J NEUROCHEM, V73, P2184

[8] Transfer of glutamine between astrocytes and neurons [J].

Bröer, S ;

Brookes, N .

JOURNAL OF NEUROCHEMISTRY, 2001, 77 (03) :705-719

[9] Glutamine uptake by neurons: Interaction of protons with system a transporters [J].

Chaudhry, FA ;

Schmitz, D ;

Reimer, RJ ;

Larsson, P ;

Gray, AT ;

Nicoll, R ;

Kavanaugh, M ;

Edwards, RH .

JOURNAL OF NEUROSCIENCE, 2002, 22 (01) :62-72

[10] Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission [J].

Chaudhry, FA ;

Reimer, RJ ;

Krizaj, D ;

Barber, D ;

Storm-Mathisen, J ;

Copenhagen, DR ;

Edwards, RH .

CELL, 1999, 99 (07) :769-780

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