Di- and heptavalent nicotinic analogues to interfere with α7 nicotinic acetylcholine receptors

被引：4

作者：

Brissonnet, Yoan ^{[1
]}

Araoz, Romulo ^{[2
,3
]}

Sousa, Rui ^{[1
]}

Percevault, Lucie ^{[1
]}

Brument, Sami ^{[1
]}

Deniaud, David ^{[1
]}

Servent, Denis ^{[3
]}

Le Questel, Jean-Yves ^{[1
]}

Lebreton, Jacques ^{[1
]}

Gouin, Sebastien G. ^{[1
]}

机构：

[1] Univ Nantes, CEISAM, CNRS, UFR Sci & Tech,UMR 6230, 2 Rue Houssiniere,BP 92208, F-44322 Nantes 3, France

[2] CNRS, NeuroPSI, UMR9197, F-91191 Gif Sur Yvette, France

[3] CEA, DRF, JOLIOT, SIMOPRO,Toxines Recepteur & Canaux Ion, F-91191 Gif Sur Yvette, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2019年 / 27卷 / 05期

关键词：

Multivalency; Nicotinic acetylcholine receptors; Multivalent nicotinics; GLYCOSIDASE INHIBITION; MULTIVALENT INHIBITORS; LECTIN RECOGNITION; BINDING-PROTEIN; LIGANDS; CYCLODEXTRINS; SELECTIVITY; PARADIGM; DOCKING; TARGETS;

D O I：

10.1016/j.bmc.2019.01.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the field of nicotinic acetylcholine receptors (nAChRs), recognized as important therapeutic targets, much effort has been dedicated to the development of nicotinic analogues to agonize or antagonize distinct homo-and heteropentamers nAChR subtypes, selectively. In this work we developed di- and heptavalent nicotinic derivatives based on ethylene glycol (EG) and cyclodextrin cores, respectively. The compounds showed a concentration dependent inhibition of acetylcholine-induced currents on alpha 7 nAChR expressed by Xenopus oocytes. Interesting features were observed with the divalent nicotinic derivatives, acting as antagonists with varied inhibitory concentrations (IC50) in function of the spacer arm length. The best divalent compounds showed a 16-fold lowered IC50 compared to the monovalent reference (12 vs 195 mu M). Docking investigations provide guidelines to rationalize these experimental findings.

引用

页码：700 / 707

页数：8

共 48 条

[1] Dualsteric GPCR targeting: a novel route to binding and signaling pathway selectivity [J].

Antony, Johannes ;

Kellershohn, Kerstin ;

Mohr-Andrae, Marion ;

Kebig, Anna ;

Prilla, Stefanie ;

Muth, Mathias ;

Heller, Eberhard ;

Disingrini, Teresa ;

Dallanoce, Clelia ;

Bertoni, Simona ;

Schrobang, Jasmin ;

Traenkle, Christian ;

Kostenis, Evi ;

Christopoulos, Arthur ;

Hoeltje, Hans-Dieter ;

Barocelli, Elisabetta ;

De Amici, Marco ;

Holzgrabe, Ulrike ;

Mohr, Klaus .

FASEB JOURNAL, 2009, 23 (02) :442-450

[2] The Neurotoxic Effect of 13,19-Didesmethyl and 13-Desmethyl Spirolide C Phycotoxins Is Mainly Mediated by Nicotinic Rather Than Muscarinic Acetylcholine Receptors [J].

Araoz, Romulo ;

Ouanounou, Gilles ;

Iorga, Bogdan I. ;

Goudet, Amelie ;

Alili, Doria ;

Amar, Muriel ;

Benoit, Evelyne ;

Molgo, Jordi ;

Servent, Denis .

TOXICOLOGICAL SCIENCES, 2015, 147 (01) :156-167

[3] Total Synthesis of Pinnatoxins A and G and Revision of the Mode of Action of Pinnatoxin A [J].

Araoz, Romulo ;

Servent, Denis ;

Molgo, Jordi ;

Iorga, Bogdan I. ;

Fruchart-Gaillard, Carole ;

Benoit, Evelyne ;

Gu, Zhenhua ;

Stivala, Craig ;

Zakarian, Armen .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (27) :10499-10511

[4] An efficient route to VEGF-like peptide porphyrin conjugates via microwave-assisted 'click-chemistry' [J].

Bakleh, M. E. ;

Sol, V. ;

Estieu-Gionnet, K. ;

Granet, R. ;

Deleris, G. ;

Krausz, P. .

TETRAHEDRON, 2009, 65 (36) :7385-7392

[5] The Protein Data Bank [J].

Berman, HM ;

Battistuz, T ;

Bhat, TN ;

Bluhm, WF ;

Bourne, PE ;

Burkhardt, K ;

Iype, L ;

Jain, S ;

Fagan, P ;

Marvin, J ;

Padilla, D ;

Ravichandran, V ;

Schneider, B ;

Thanki, N ;

Weissig, H ;

Westbrook, JD ;

Zardecki, C .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2002, 58 :899-907

[6] Multivalent glycoconjugates as anti-pathogenic agents [J].

Bernardi, Anna ;

Jimenez-Barbero, Jesus ;

Casnati, Alessandro ;

De Castro, Cristina ;

Darbre, Tamis ;

Fieschi, Franck ;

Finne, Jukka ;

Funken, Horst ;

Jaeger, Karl-Erich ;

Lahmann, Martina ;

Lindhorst, Thisbe K. ;

Marradi, Marco ;

Messner, Paul ;

Molinaro, Antonio ;

Murphy, Paul V. ;

Nativi, Cristina ;

Oscarson, Stefan ;

Penades, Soledad ;

Peri, Francesco ;

Pieters, Roland J. ;

Renaudet, Olivier ;

Reymond, Jean-Louis ;

Richichi, Barbara ;

Rojo, Javier ;

Sansone, Francesco ;

Schaeffer, Christina ;

Turnbull, W. Bruce ;

Velasco-Torrijos, Trinidad ;

Vidal, Sebastien ;

Vincent, Stephane ;

Wennekes, Tom ;

Zuilhof, Han ;

Imberty, Anne .

CHEMICAL SOCIETY REVIEWS, 2013, 42 (11) :4709-4727

[7] CYCLODEXTRIN CHEMISTRY - SELECTIVE MODIFICATION OF ALL PRIMARY HYDROXYL-GROUPS OF ALPHA-CYCLODEXTRINS AND BETA-CYCLODEXTRINS [J].

BOGER, J ;

CORCORAN, RJ ;

LEHN, JM .

HELVETICA CHIMICA ACTA, 1978, 61 (06) :2190-2218

[8] Heptyl -D-Mannosides Grafted on a -Cyclodextrin Core To Interfere with Escherichia coli Adhesion: An In Vivo Multivalent Effect [J].

Bouckaert, Julie ;

Li, Zhaoli ;

Xavier, Catarina ;

Almant, Mehdi ;

Caveliers, Vicky ;

Lahoutte, Tony ;

Weeks, Stephen D. ;

Kovensky, Jose ;

Gouin, Sebastien G. .

CHEMISTRY-A EUROPEAN JOURNAL, 2013, 19 (24) :7847-7855

[9] Topological Effects and Binding Modes Operating with Multivalent Iminosugar-Based Glycoclusters and Mannosidases [J].

Brissonnet, Yoan ;

Ortiz Mellet, Carmen ;

Morandat, Sandrine ;

Garcia Moreno, M. Isabel ;

Deniaud, David ;

Matthews, Susan E. ;

Vidal, Sebastien ;

Sestak, Sergej ;

El Kirat, Karim ;

Gouin, Sebastien G. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (49) :18427-18435

[10] Design and Characterization of Superpotent Bivalent Ligands Targeting Oxytocin Receptor Dimers via a Channel-Like Structure [J].

Busnelli, Marta ;

Kleinau, Gunnar ;

Muttenthaler, Markus ;

Stoev, Stoytcho ;

Manning, Maurice ;

Bibic, Lucka ;

Howell, Lesley A. ;

McCormick, Peter J. ;

Di Lascio, Simona ;

Braida, Daniela ;

Sala, Mariaelvina ;

Rovati, G. Enrico ;

Bellini, Tommaso ;

Chini, Bice .

JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (15) :7152-7166

← 1 2 3 4 5 →