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

被引：133

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.

引用

页码：1111 / 1118

页数：8