Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes: Discovery of nanomolar, nonselective, and use-dependent antagonists

Journal of Medicinal Chemistry

Volumn 53, Issue 20, 2010, Pages 7441-7451

  Frølund, Sidsel ^a   Bella, Angelo ^a   Kristensen, Anders S ^a   Ziegler, Hanne L ^a   Witt, Matthias ^b   Olsen, Christian A ^a   Strømgaard, Kristian ^a   Franzyk, Henrik ^a   Jaroszewski, Jerzy W ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b BRUKER DALTONIK GMBH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; AMPA RECEPTOR; IONOTROPIC RECEPTOR; IONOTROPIC RECEPTOR ANTAGONIST; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2A; PHILANTHOTOXIN; PHILANTHOTROXIN DERIVATIVE; SPERMINE; UNCLASSIFIED DRUG; WASP VENOM; AMINO ACID RECEPTOR BLOCKING AGENT; DELTA-PHILANTHOTOXIN; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PHENOL DERIVATIVE; PHILANTHOTOXIN 343; POLYAMINE; PROTEIN SUBUNIT;

ARTICLE; DRUG SYNTHESIS; ELECTROPHYSIOLOGY; FEMALE; IC 50; NONHUMAN; OOCYTE; RECEPTOR BLOCKING; SOLID PHASE SYNTHESIS; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; VOLTAGE CLAMP; XENOPUS LAEVIS; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; PATCH CLAMP TECHNIQUE; PHYSIOLOGY; PROTEIN SUBUNIT; SYNTHESIS;

ANIMALS; EXCITATORY AMINO ACID ANTAGONISTS; FEMALE; OOCYTES; PATCH-CLAMP TECHNIQUES; PHENOLS; POLYAMINES; PROTEIN SUBUNITS; RECEPTORS, AMPA; RECEPTORS, N-METHYL-D-ASPARTATE; STRUCTURE-ACTIVITY RELATIONSHIP; WASP VENOMS; XENOPUS LAEVIS;

EID: 77958507088     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100886h     Document Type: Article

References (42)

1. Blennow, K.; de Leon, M. J.; Zetterberg, H. Alzheimers disease Lancet 2006, 368, 387-403
2. Querfurth, H. W.; LaFerla, F. M. Alzheimers disease N. Eng. J. Med. 2010, 262, 329-344
3. Citron, M. Alzheimers disease: strategies for disease modification Nature Rev. Drug Discovery 2010, 9, 387-398
4. Lleo, A.; Greenberg, S. M.; Growdon, J. H. Current pharmacotherapy for Alzheimers disease Ann. Rev. Med. 2006, 57, 513-533
5. Schliebs, R.; Arendt, T. The significance of the cholinergic system in the brain during aging and in Alzheimers disease J. Neural Transm. 2006, 113, 1625-1644
6. Munoz-Torrero, D. Acetylcholinesterase inhibitors as disease-modifying therapies for Alzheimers disease Curr. Med. Chem. 2008, 15, 2433-2455
7. Lipton, S. A. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond Nature Rev. Drug Discovery 2006, 6, 160-170
8. Parsons, C. G.; Stoffler, A.; Danysz, W. Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system - too little activation is bad, too much is even worse Neuropharmacology 2007, 53, 699-723
9. McKeage, K. Memantine, a review of its use in moderate to severe Alzheimers disease CNS Drugs 2009, 23, 881-897
10. Van Marum, R. J. Update on the use of memantine in Alzheimers disease Neuropsychiatr. Dis. Treat. 2009, 5, 237-247
11. Strømgaard, K.; Jensen, L. S.; Vogensen, S. B. Polyamine toxins: development of selective ligands for ionotropic receptors Toxicon 2005, 45, 249-254
12. Eldefrawi, A. T.; Eldefrawi, M. E.; Konno, K.; Mansour, N. A.; Nakanishi, K.; Oltz, E.; Usherwood, P. N. Structure and synthesis of a potent glutamate receptor antagonist in wasp venom Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 4910-4913
13. Dingledine, R.; Borges, K.; Bowie, D.; Traynelis, S. F. The glutamate receptor ion channels Pharmacol. Rev. 1999, 51, 7-61
14. Wollmuth, L.; Sobolevsky, A. Structure and gating of the glutamate receptor ion channel Trends Neurosci. 2004, 27, 321-328
15. Mayer, M. Glutamate receptors at atomic resolution Nature 2006, 440, 456-462
16. Strømgaard, K.; Brier, T. J.; Andersen, K.; Mellor, I. R.; Saghyan, A.; Tikhonov, D.; Usherwood, P. N. R.; Krogsgaard-Larsen, P.; Jaroszewski, J. W. Solid-phase synthesis and biological evaluation of a combinatorial library of philanthotoxin analogues J. Med. Chem. 2000, 43, 4526-4533 (Pubitemid 32046877)
17. Chhabra, S. R.; Khan, A. N.; Bycroft, B. W. Solid-phase synthesis of polyamines using a Dde-linker: philanthotoxin-4.3.3 via an on-resin Mitsunobu reaction Tetrahedron Lett. 2000, 41, 1099-1102
18. Strømgaard, K.; Andersen, K.; Ruhland, T.; Krogsgaard-Larsen, P.; Jaroszewski, J. W. A versatile method for solid-phase synthesis of polyamines: neuroactive polyamine toxins as example Synthesis 2001, 877-884
19. Kan, T.; Kobayashi, H.; Fukuyama, T. Highly versatile synthesis of polyamines by Ns-strategy on a novel trityl chloride resin Synlett 2002, 1338-1340
20. Andersen, T. F.; Strømgaard, K. Synthesis of Polyamine Toxins. An improved alkylation procedure Tetrahedron Lett. 2004, 45, 7929-7933
21. Olsen, C. A.; Witt, M.; Jaroszewski, J. W.; Franzyk, H. Diols as building blocks in solid-phase synthesis of polyamine toxins by Fukuyama-Mitsunobu alkylation Synlett 2004, 473-476
22. Olsen, C. A.; Witt, M.; Jaroszewski, J. W.; Franzyk, H. Solid-phase synthesis of rigid acylpolyamines using temporary N -4,4′-dimethoxytrityl protection in the presence of trityl linkers J. Org. Chem. 2004, 69, 6149-6152
23. Jørgensen, M. R.; Jaroszewski, J. W.; Witt, M.; Franzyk, H. On-resin carboxy group activation of -amino acids in solid-phase synthesis of philanthotoxin analogues Synthesis 2005, 2687-2694
24. Olsen, C. A.; Franzyk, H.; Jaroszewski, J. W. N -Alkylation reactions and indirect formation of amino functionalities in solid-phase synthesis Synthesis 2005, 2631-2653
25. Wellendorph, P.; Jaroszewski, J. W.; Hansen, S. H.; Franzyk, H. A sequential high-yielding large-scale solution-method for synthesis of philanthotoxin analogues Eur. J. Med. Chem. 2003, 38, 117-122
26. Olsen, C. A.; Mellor, I. R.; Wellendorph, P.; Usherwood, P. N. R.; Witt, M.; Franzyk, H.; Jaroszewski, J. W. Tuning wasp toxin structure for nicotinic receptor antagonism: cyclohexylalanine-containing analogues as potent and voltage-dependent blockers ChemMedChem 2006, 1, 303-305
27. Jørgensen, M. R.; Olsen, C. A.; Mellor, I. R.; Usherwood, P. N. R.; Witt, M.; Jaroszewski, J. W.; Franzyk, H. The effects of conformational constraints and steric bulk in the amino acid moiety of philanthotoxins on AMPAR antagonism J. Med. Chem. 2005, 48, 56-70
28. α-Fmoc- Tyr-OPfp for bidirectional solid-phase synthesis Org. Lett. 2005, 7, 1703-1706
29. Strømgaard, K.; Brierley, M. J.; Andersen, K.; Sløk, F. A; Mellor, I. R.; Usherwood, P. N. R.; Krogsgaard-Larsen, P.; Jaroszewski, J. W. Analogues of neuroactive polyamine wasp toxins that lack inner basic sites exhibit enhanced antagonism toward a muscle-type mammalian nicotinic acetylcholine receptor J. Med. Chem. 1999, 42, 5224-5234
30. 2+-permeable AMPA receptors J. Med. Chem. 2002, 45, 5745-5754
31. Jaroszewski, J. W.; Matzen, L.; Frølund, B.; Krogsgaard-Larsen, P. Neuroactive polyamine wasp toxins: nuclear magnetic resonance spectroscopic studies of the protolytic properties of philanthotoxin-343 J. Med. Chem. 1996, 39, 515-521
32. 13C NMR spectroscopy Magn. Reson. Chem. 2006, 44, 1013-1022
33. Kallimopoulos, R.; Bukownik, K.; Nakanishi, P.; Usherwood, A.; Eldefrawi, A.; Eldefrawi, M. Structure-activity relationships of philanthotoxin analogs and polyamines on N -methyl- d -aspartate and nicotinic acetylcholine receptors J. Pharmacol. Exp. Ther. 1990, 254, 764-773
34. Olsen, C. A.; Witt, M.; Franzyk, H.; Jaroszewski, J. W. Solid-phase synthesis of neuroactive spider-wasp hybrid toxin analogues using a backbone amide linker Tetrahedron Lett. 2007, 48, 405-408
35. Nelson, J. K.; Frølund, S. U.; Tikhonov, D. B.; Kristensen, A. S.; Strømgaard, K. Synthesis and biology of argiotoxin-636 and analogues: selective antagonists for ionotropic glutamate receptors Angew. Chem., Int. Ed. 2009, 49, 3087-3091
36. Drake, B.; Patek, M.; Lebl, M. A convenient preparation of monosubstituted N, N ′-di(Boc)-protected guanidines Synthesis 1994, 579-582
37. Bonke, G.; Vedel, L.; Witt, M.; Jaroszewski, J. W.; Olsen, C. A.; Franzyk, H. Dimeric building blocks for solid-phase synthesis of α-peptide-β-peptoid chimeras Synthesis 2008, 2381-2390
38. --[[2-Trimethylsilyl)ethoxy] carbonyl] derivatives of tri- l -lysine and tetra- l -lysine as potential intermediates in the block polymer synthesis of macromolecular drug conjugates J. Org. Chem. 1989, 54, 5551-5558
39. Ha, S.; Chang, E.; Lo, M.-C.; Men, H.; Park, P.; Ge, M.; Walker, S. The kinetic characterization of Escherichia coli MurG using synthetic substrate analogues J. Am. Chem. Soc. 1999, 121, 8415-8426 (Pubitemid 29453375)
40. Bresink, I.; Benke, T. A.; Collett, V. J.; Seal, A. J.; Parsons, C. G.; Henley, J. M.; Collingridge, G. L. Effects of memantine on recombinant rat NMDA receptors expressed in HEK 293 cells Br. J. Pharmacol. 1996, 119, 195-204
41. Gilling, K. E.; Jatzke, C.; Hechenberger, M.; Parsons, C. G. Potency, voltage-dependency, agonist concentration-dependency, blocking kinetics and partial untrapping of the uncompetitive N -methyl- d -aspartate (NMDA) channel blocker memantine at human NMDA (GluN1/GluN2A) receptors Neuropharmacology 2009, 56, 866-875
42. Dravid, S. M.; Erreger, K.; Yuan, H.; Nicholson, K.; Le, P.; Lyuboslavsky, P.; Almonte, A.; Murray, E.; Mosely, C.; Barber, J.; French, A.; Balster, R.; Murray, T. F.; Traynelis, S. F. Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block J. Physiol. 2007, 581, 107-128