Photoswitchable Serotonins for Optical Control of the 5-HT2A Receptor

被引：28
|
作者：
Morstein, Johannes [1 ]
Romano, Giovanna [2 ,3 ]
Hetzler, Belinda E. [1 ]
Plante, Ambrose [2 ,3 ]
Haake, Caleb [1 ]
Levitz, Joshua [2 ,3 ]
Trauner, Dirk [1 ]
机构：
[1] NYU, Dept Chem, New York, NY 10003 USA
[2] Weill Cornell Med, Physiol Biophys & Syst Biol Grad Program, New York, NY 10065 USA
[3] Weill Cornell Med, Dept Biochem, New York, NY 10065 USA
来源：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2022年 / 61卷 / 18期
基金：
美国国家科学基金会;
关键词：
GPCR; Photopharmacology; Photoswitch; Serotonin; SNAP Tag; AGONIST; DERIVATIVES;
D O I：
10.1002/anie.202117094
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Serotonin receptors play central roles in neuromodulation and are critical drug targets for psychiatric disorders. Optical control of serotonin receptor subtypes has the potential to greatly enhance our understanding of the spatiotemporal dynamics of receptor function. While other neuromodulatory receptors have been successfully rendered photoswitchable, reversible photocontrol of serotonin receptors has not been achieved, representing a major gap in GPCR photopharmacology. Herein, we develop the first tools that allow for such control. Azo5HT-2 shows light-dependent 5-HT2AR agonism, with greater activity in the cis-form. Based on docking and test compound analysis, we also develop photoswitchable orthogonal, remotely-tethered ligands (PORTLs). These BG-Azo5HTs provide rapid, reversible, and repeatable optical control following conjugation to SNAP-tagged 5-HT2AR. Overall, this study provides a foundation for the broad extension of photopharmacology to the serotonin receptor family.
引用
收藏
页数：7
相关论文
共 50 条
  • [41] BDNF downregulates 5-HT2A receptor protein levels in hippocampal cultures
    Trajkovska, V.
    Santini, M. A.
    Marcussen, A. B.
    Thomsen, M. S.
    Hansen, H. H.
    Mikkelsen, J. D.
    Arneberg, L.
    Kokaia, M.
    Knudsen, G. M.
    Aznar, S.
    NEUROCHEMISTRY INTERNATIONAL, 2009, 55 (07) : 697 - 702
  • [42] 5-HT2A receptor gene polymorphisms in Croatian subjects with autistic disorder
    Hranilovic, Dubravka
    Blazevic, Sofia
    Babic, Marina
    Smurinic, Maja
    Bujas-Petkovic, Zorana
    Jernej, Branimir
    PSYCHIATRY RESEARCH, 2010, 178 (03) : 556 - 558
  • [43] Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine
    Arranz, MJ
    Collier, DA
    Munro, J
    Sham, P
    Kirov, G
    Sodhi, M
    Roberts, G
    Price, J
    Kerwin, RW
    NEUROSCIENCE LETTERS, 1996, 217 (2-3) : 177 - 178
  • [44] Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity
    Kaplan, Anat Levit
    Confair, Danielle N.
    Kim, Kuglae
    Barros-Alvarez, Ximena
    Rodriguiz, Ramona M.
    Yang, Ying
    Kweon, Oh Sang
    Che, Tao
    McCorvy, John D.
    Kamber, David N.
    Phelan, James P.
    Martins, Luan Carvalho
    Pogorelov, Vladimir M.
    DiBerto, Jeffrey F.
    Slocum, Samuel T.
    Huang, Xi-Ping
    Kumar, Jain Manish
    Robertson, Michael J.
    Panova, Ouliana
    Seven, Alpay B.
    Wetsel, Autumn Q.
    Wetsel, William C.
    Irwin, John J.
    Skiniotis, Georgios
    Shoichet, Brian K.
    Roth, Bryan L.
    Ellman, Jonathan A.
    NATURE, 2022, 610 (7932) : 582 - +
  • [45] 5-HT2A receptor activation is necessary for CO2-induced arousal
    Buchanan, Gordon F.
    Smith, Haleigh R.
    MacAskill, Amanda
    Richerson, George B.
    JOURNAL OF NEUROPHYSIOLOGY, 2015, 114 (01) : 233 - 243
  • [46] Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential
    Wallach, Jason
    Cao, Andrew B.
    Calkins, Maggie M.
    Heim, Andrew J.
    Lanham, Janelle K.
    Bonniwell, Emma M.
    Hennessey, Joseph J.
    Bock, Hailey A.
    Anderson, Emilie I.
    Sherwood, Alexander M.
    Morris, Hamilton
    de Klein, Robbin
    Klein, Adam K.
    Cuccurazzu, Bruna
    Gamrat, James
    Fannana, Tilka
    Zauhar, Randy
    Halberstadt, Adam L.
    Mccorvy, John D.
    NATURE COMMUNICATIONS, 2023, 14 (01)
  • [47] 5-HT2A receptor density is decreased in the at-risk mental state
    Hurlemann, Rene
    Matusch, Andreas
    Kuhn, Kai-Uwe
    Berning, Julia
    Elmenhorst, David
    Winz, Oliver
    Kolsch, Heike
    Zilles, Karl
    Wagner, Michael
    Maier, Wolfgang
    Bauer, Andreas
    PSYCHOPHARMACOLOGY, 2008, 195 (04) : 579 - 590
  • [48] Role of mGlu2 in the 5-HT2A receptor-dependent antipsychotic activity of clozapine in mice
    Hideshima, Kelsey S.
    Hojati, Ashkhan
    Saunders, Justin M.
    On, Doan M.
    Revenga, Mario de la Fuente
    Shin, Jong M.
    Sanchez-Gonzalez, Ana
    Dunn, Cassandra M.
    Pais, Alexander B.
    Pais, Anthony C.
    Miles, Michael F.
    Wolstenholme, Jennifer T.
    Gonzalez-Maeso, Javier
    PSYCHOPHARMACOLOGY, 2018, 235 (11) : 3149 - 3165
  • [49] Effects of psilocybin, the 5-HT2A receptor agonist TCB-2, and the 5-HT2A receptor antagonist M100907 on visual attention in male mice in the continuous performance test
    Rahbarnia, Arya
    Li, Zhaoxia
    Fletcher, Paul J.
    PSYCHOPHARMACOLOGY, 2023,
  • [50] Evidence that genetic variation in 5-HT transporter expression is linked to changes in 5-HT2A receptor function
    Jennings, K. A.
    Sheward, W. J.
    Harmar, A. J.
    Sharp, T.
    NEUROPHARMACOLOGY, 2008, 54 (05) : 776 - 783
12345