¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• (β2AR) using either a 19F-BTFA [29] or a 19F-TFET [36] tag were used to explore the differential long range conformational effects induced by agonists, inverse agonists, and partial agonists on GPCR signalling. As exemplified by Liu et al. [36], in the case of multiply site-specific labelled 19F-TFET

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• applied, photopharmacology has drawn great interest for studies of crucial biological processes in a range of fields, from neuroscience [5][6] and G-protein-coupled receptor (GPCR) function [7][8] to antibiotic research [9]. Particularly in the context of MT biology, photopharmacology is an attractive

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• challenges to be solved. Hydrophilic and hydrophobic interactions with the unpolar lipid layer make the tendency to yield suitable crystals even more difficult. Nevertheless, Palczewski and co-workers were able to crystallise the first GPCR (G-protein-coupled receptor) in 2000 confirming the previously

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• VUF16216, a compound we have previously communicated as a small-molecule efficacy photoswitch for the peptidergic chemokine GPCR CXCR3. A series of photoswitchable azobenzene ligands was prepared through various synthetic strategies and multistep syntheses. Photochemical and pharmacological properties were

• superfamily of membrane proteins that regulate many physiological processes [12]. Despite the high relevance of GPCRs both functionally and as a drug target [12], the first synthetic GPCR photochromic small-molecule ligands appeared only five years ago [13][14][15]. Since then, photopharmacology has been

• ligands [10]. The ensuing photochromic GPCR ligands are usually orthosteric and the photoswitching generally affects the functional potency [4][11][23] and/or the binding affinity [3][4][5][11] of the ligand (Figure 1A). However, as mentioned, GPCRs that endogenously bind large molecules (large peptides

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• been identified as fast and efficiently internalizing GPCR in those cells upon agonist binding [29][30]. The NPY Y1 receptor subtype for these reasons is a very promising molecular target to be addressed by selective peptide–drug conjugates (PDCs), notably for cancer treatment or diagnosis. However

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• obtained in the absence of its epimer, epi-8. Moreover, the chemical entities described herein offer opportunities for studies in glycobiology, biomedicinal chemistry and drug design. The use of these compounds as starting material to access new small ligands as GPCR modulators is ongoing in our

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• - and hardware have made MD simulations a powerful tool in GPCR research. This is important because GPCRs are targeted by approximately half of the drugs on the market, so that computer-aided drug design plays a major role in GPCR research. Keywords: computer-aided drug design; GPCR; metadynamicxs

• atomistic resolution are needed to decipher the intimate details of the modes of action of GPCRs. X-ray crystallographic studies on GPCRs are, however, fraught with difficulties [6]. The structure of rhodopsin, the first GPCR X-ray structure, was published in 2000 [7], was not followed by the second, the β2

• -adrenergic receptor, until 2007 [8]. Figure 1 shows the growth in the number of GPCR structures from 2000–2016. After a very slow start, structures for on average six new receptors per year have been becoming available in the last five years. Each of these structures is a significant experimental achievement

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• to the identification of new dual NK1/NK2 antagonists [12], as shown in Figure 2 (B). In 2003, the pharmaceutical company Zentaris patented a series of tetrahydrocarbazole derivatives as ligands for G-protein-coupled receptors (GPCR), and in particular as antagonists of the gonadotropin-releasing

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• ), naltrindole [10], β-funaltrexamine [11], and the NOP antagonist C-24 [16]. Beyond opioids, ionic H-bonds to Asp3.32 are conserved across biogenic amine receptors; indeed, this residue3.32 interacts with the ligand in almost all GPCR crystal structures reported to date [17]. In summary, 1 appears to bind

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature. Keywords: epoxides; GPCR; NPS 2143; nucleophilic aromatic substitution; pyrylium chemistry; Introduction The first G-protein-coupled receptors

• major classes (A, B and C) of which the rhodopsin-like class A is the largest and most diverse, and which has been well-studied and subject to drug targeting [3]. GPCR class C is much smaller and comprises only 22 known receptors including eight metabotropic glutamate (mGlu) receptors, two γ