Clickable photoaffinity ligands for the human serotonin transporter based on the selective serotonin reuptake inhibitor (S)-citalopram.
Clickable photoaffinity ligands for the human serotonin transporter based on the selective serotonin reuptake inhibitor (S)-citalopram.
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DOI：
10.1016/j.bmcl.2018.09.029
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发表时间：
2018-11-15
影响因子：
2.7
通讯作者：
Lapinsky DJ
中科院分区：
文献类型：
--
作者：
Yarravarapu N;Geffert L;Surratt CK;Cascio M;Lapinsky DJ
到目前为止，针对人类5-羟色胺转运体(HSERT)的光亲和配体的开发一直是基于放射性同位素(即~3H或125I)的，hSERT是参与抑郁症和焦虑等疾病状态的关键蛋白。相反，这封信强调了选择性5-羟色胺再摄取抑制物(S)的三个衍生物-西酞普兰，它们经过合理设计和合成，含有通过光亲和标记捕捉蛋白质靶标的光反应性二苯甲酮或芳基叠氮，以及用于点击化学蛋白质组学的末端炔或脂肪叠氮化物。具体地说，可点击的二苯甲酮(S)-西酞普兰光电探针6(hSERTki=0.16nM)在hSERT上显示出比(S)-西酞普兰(hSERTKi=1.77 nM)高11倍的结合亲和力，随后被证明成功地进行了串联光亲和标记-双正交结合。由于可点击光电探针可用于各种应用，取决于在光亲和标记之后点击化学连接的报告，光电探针6有望在结构-功能研究和涉及hSERT的其他研究应用中找到价值(例如，成像)。
To date, the development of photoaffinity ligands targeting the human serotonin transporter (hSERT), a key protein involved in disease states such as depression and anxiety, have been radioisotope-based (i.e., 3H or 125I). This letter instead highlights three derivatives of the selective serotonin reuptake inhibitor (SSRI) (S)-citalopram that were rationally designed and synthesized to contain a photoreactive benzophenone or an aryl azide for protein target capture via photoaffinity labeling and a terminal alkyne or an aliphatic azide for click chemistry-based proteomics. Specifically, clickable benzophenone-based (S)-citalopram photoprobe 6 (hSERT Ki = 0.16 nM) displayed 11-fold higher binding affinity at hSERT when compared to (S)-citalopram (hSERT Ki = 1.77 nM), and was subsequently shown to successfully undergo tandem photoaffinity labeling-biorthogonal conjugation using purified hSERT. Given clickable photoprobes can be used for various applications depending on which reporter is attached by click chemistry subsequent to photoaffinity labeling, photoprobe 6 is expected to find value in structure-function studies and other research applications involving hSERT (e.g., imaging).
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影响因子：
2.8
作者：
Bandyopadhyay, Saibal;Bong, Dennis
通讯作者：
Bong, Dennis
DOI：
10.1111/j.1600-0773.1997.tb00396.x
发表时间：
1997-04-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
Plenge, P;Mellerup, ET
通讯作者：
Mellerup, ET
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
6.1
作者：
REHAVI, M;TRACER, H;PAUL, SM
通讯作者：
PAUL, SM
影响因子：
3.7
作者：
Kirmeier T;Gopalakrishnan R;Gormanns V;Werner AM;Cuboni S;Rudolf GC;Höfner G;Wanner KT;Sieber SA;Schmidt U;Holsboer F;Rein T;Hausch F
通讯作者：
Hausch F