发现小说peptidic多巴胺转运蛋白配体通过筛选位置扫描组合hexapeptide图书馆。

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Rothman RB、鲍曼MH Dersch厘米,Appel J, Houghten RA

发现小说peptidic多巴胺转运蛋白配体通过筛选位置扫描组合hexapeptide图书馆。

Synapse。1999年9月1;33 (3):239 - 46。

PubMed ID

10420171 (在PubMed

]

文摘

可卡因的急性加固效应被认为一些由于可卡因绑定多巴胺(DA),抑制哒吸收,增加突触哒水平在中脑边缘系统。以外的其他数据显示,神经递质DA有助于可卡因强化和上瘾。这些因素说明了需要额外的研究工具来测试“DA”假说。必威国际appOne strategy is to identify drugs which bind to the DA transporter (DAT ligands) but which do not inhibit DA uptake as effectively as cocaine. The purpose of the present study was to identify members of a novel structural class of DAT ligands and to characterize their interactions at the DA transporter. A positional scanning hexapeptide D-amino acid library was screened for inhibition of [(125)I]RTI-55 binding to rat caudate DA transporters. Based on the results, 12 peptides were synthesized. All 12 peptides inhibited [(125)I]RTI-55 binding to DA transporters with IC(50) values, which ranged from 1.8 microM to 12 microM. The two most potent peptides (TPI-669-1 and TPI-669-4) were prepared in larger quantities and were characterized further for activity at the DAT and 5-HT transporter. Both peptides inhibited DA and 5-HT uptake and transporter binding with IC(50)/K(i) values in the low micromolar range. In vivo microdialysis studies demonstrated that both peptides increase extracellular DA and 5-HT in the nucleus accumbens of rats. These data demonstrate that peptides can function as inhibitors of biogenic amine transport. Future work will focus on developing more potent and selective peptides. Published 1999 Wiley-Liss, Inc.

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药物靶点

药物	目标	类	生物	药理作用	行动
可卡因	Sodium-dependent多巴胺转运体	蛋白质	人类	是的	抑制剂	细节