Core B: Synthetic Chemistry Core

化学核心的目标是在获取方面为PPG活动提供全面支持 用于研究配体门控的全身麻醉剂结合位点的合成分子探针 γ-氨基丁酸（GABAA）、乙酰胆碱和5-羟色胺受体。探针将代表 与这些受体相互作用的四种主要麻醉剂，并将用于研究 对应这些受体上的多个结合位点。我们的结构和 合成设计是产生具有最小结构改变的可光活化的类似物， 结合亲和力，并确保与母体分子的结合模式类似，并允许 合成具有最高比放射性的放射性标记分子。我们将合成 （i）丙泊酚，GABAA受体配体和有效的 （ii）巴比妥酸，GABAA和烟碱乙酰胆碱受体的配体; (iii)长链脂族和芳族醇，在所有分子上具有结合位点的配体， 超家族;和（iv）依托咪酯，另一种结合在GABAA受体的麻醉位点的有效配体。 此外，当需要时，我们将重新合成先前已使用的任何所需配体。 PPG。核心的领导权已由芝加哥的布鲁齐克博士接任。核心的一小部分 仍存放于澳门总督府，以派发及保存现有的光印标签。行政上 核心是由项目总监作为PI和伊利诺伊大学芝加哥分校的顾问组成的。 相关性（见说明）：

The goal of the Chemistry Core is to provide a complete support of the PPG activities in terms of access to synthetic molecular probes to be used for the investigation of general anesthetic binding sites of ligand-gated receptors of y-aminobutyric acid (GABAA) acetylcholine and serotonin . The probes will represent analogs of four major classes of anesthetics that interact with these receptors, and will be used for studying the corresponding multiple binding sites on these receptors. The most important aspects of our structural and synthetic design is to produce photoactivatable analogs with minimal structure alteration to retain high binding affinity and to ensure the analogous modes of binding to those of the parent molecules, and to permit synthesis of the radiolabeled molecules with the highest specific radioactivity possible. We will synthesize analogs of the following groups of receptor ligands: (i) propofol, a GABAA receptor ligand and a potent clinically used general anesthetic; (ii) barbituric acid, a ligand of GABAA and nicotinic acetylcholine receptors; (iii) long-chain aliphatic and aromatic alcohols, ligands that have binding sites on all members of the superfamily; and (iv) etomidate, another potent ligand that binds in the anesthetic site of GABAA receptors. In addition, when needed, we will resynthesize any needed ligand that has previously been used by the PPG. The leadership of the Core has been assumed by Dr. Bruzik in Chicago. A small part of the Core remains at MGH for the distribution and maintenance of stocks of existing photolabels. Administratively, the Core is structured with the Program Director as PI and a subcontract to the University of Illinois, Chicago. RELEVANCE (See Instmctions):