基于2β-甲氧羰基-3β-联苯基托烷设计并合成一种用于多巴胺和5-羟色胺转运体的新型光亲和配体。
Design and synthesis of a novel photoaffinity ligand for the dopamine and serotonin transporters based on 2beta-carbomethoxy-3beta-biphenyltropane.
作者信息
Newman Amy Hauck, Cha Joo Hwan, Cao Jianjing, Kopajtic Theresa, Katz Jonathan L, Parnas M Laura, Vaughan Roxanne, Lever John R
机构信息
Medicinal Chemistry and Psychobiology Sections, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health/DHHS, Baltimore, MD, USA.
出版信息
J Med Chem. 2006 Nov 2;49(22):6621-5. doi: 10.1021/jm0603973.
Tropane-based photoaffinity ligands covalently bind to discrete points of attachment on the dopamine transporter (DAT). To further explore structure-activity relations, a ligand in which the photoactivated group was extended from the 3-position of the tropane ring was synthesized from cocaine via a Stille or Suzuki coupling strategy. 3-(4'-Azido-3'-iodo-biphenyl-4-yl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid methyl ester (11; K(i) = 15.1 +/- 2.2 nM) demonstrated high binding affinity for the DAT. Moreover, this compound showed moderate binding affinity for the serotonin transporter (SERT, K(i) = 109 +/- 14 nM), suggesting the potential utility of [(125)I]11 in both DAT and SERT protein structure studies.
基于托烷的光亲和配体与多巴胺转运体（DAT）上离散的附着点共价结合。为了进一步探索构效关系，通过Stille或Suzuki偶联策略从可卡因合成了一种光活化基团从托烷环的3位延伸的配体。3-(4'-叠氮基-3'-碘-联苯-4-基)-8-甲基-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯（11；K(i)=15.1±2.2 nM）对DAT表现出高结合亲和力。此外，该化合物对5-羟色胺转运体（SERT，K(i)=109±14 nM）表现出中等结合亲和力，表明[(125)I]11在DAT和SERT蛋白质结构研究中均具有潜在用途。
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