Allosteric inhibition of g-protein coupled receptor oligomerization: Strategies and challenges for drug development

Current Topics in Medicinal Chemistry

Volumn 14, Issue 15, 2014, Pages 1842-1863

  Hurevich, Mattan ^a   Talhami, Alaa ^a   Shalev, Deborah E ^a,b   Gilon, Chaim ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b Azrieli College of Engineering   (Israel)

Author keywords

Allosteric inhibition; Chemokine receptors; GPCR inhibition; GPCR oligomerization; GPCR GPCR interactions; Gprotein coupled receptors; Helix mimetic

Indexed keywords

ANGIOTENSIN 1 RECEPTOR; ANGIOTENSIN 2 RECEPTOR; BETA 2 ADRENERGIC RECEPTOR; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; CYAN FLUORESCENT PROTEIN; CYCLOPEPTIDE; G PROTEIN COUPLED RECEPTOR; GREEN FLUORESCENT PROTEIN; HETERODIMER; HOMODIMER; MATING HORMONE ALPHA FACTOR RECEPTOR; MONOCYTE CHEMOTACTIC PROTEIN 3; RANTES; STAT PROTEIN; SYNTHETIC PEPTIDE; YELLOW FLUORESCENT PROTEIN; CHEMOKINE RECEPTOR; LIGAND; MOLECULAR LIBRARY; PEPTIDOMIMETIC AGENT; PROTEIN BINDING;

ALLOSTERISM; ARTICLE; BIOLUMINESCENCE RESONANCE ENERGY TRANSFER; CELLULAR DISTRIBUTION; CLUSTER ANALYSIS; CRYSTAL STRUCTURE; CYCLIZATION; DIMERIZATION; DRUG DESIGN; DRUG SYNTHESIS; EXCITATION; FLUORESCENCE RECOVERY AFTER PHOTOBLEACHING; FLUORESCENCE RESONANCE ENERGY TRANSFER; IMMUNOPRECIPITATION; INTERNALIZATION; LIGAND BINDING; MOLECULAR DOCKING; MUTAGENESIS; OLIGOMERIZATION; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; RECEPTOR BINDING ASSAY; RECEPTOR BLOCKING; RING CLOSING METATHESIS; STRUCTURE ACTIVITY RELATION; WESTERN BLOTTING; X RAY CRYSTALLOGRAPHY; AGONISTS; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; GENE EXPRESSION REGULATION; GENETICS; HUMAN; METABOLISM; MOLECULAR LIBRARY; PHARMACOLOGY; PROTEIN MULTIMERIZATION; SIGNAL TRANSDUCTION; SYNTHESIS;

ALLOSTERIC REGULATION; ALLOSTERIC SITE; DRUG DESIGN; GENE EXPRESSION REGULATION; HUMANS; LIGANDS; MODELS, MOLECULAR; PEPTIDOMIMETICS; PROTEIN BINDING; PROTEIN MULTIMERIZATION; RECEPTORS, CHEMOKINE; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84925940621     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026614666140901130843     Document Type: Article

References (156)

1. Szidonya, L.; Cserzo, M.; Hunyady, L. Dimerization and oligomerization of G-protein-coupled receptors: debated structures with established and emerging functions. J. Endocrinol., 2008, 196(3), 435-453.
2. Thelen, M.; Munoz, L. M.; Rodriguez-Frade, J. M.; Mellado, M. Chemokine receptor oligomerization: functional considerations. Curr. Opin. Pharmacol., 2010, 10(1), 38-43.
3. Rivero-Müller, A.; Jonas, K. C.; Hanyaloglu, A. C.; Huhtaniemi, I.; Jesus, G., and Francisco, Ciruela. In Progress in Molecular Biology and Translational Science; Jesus, G.; and Francisco, Ciruela, Ed.; Academic Press, 2013, p 163-185.
4. Limbird, L. E.; Lefkowitz, R. J. Negative cooperativity among beta-adrenergic receptors in frog erythrocyte membranes. J. Biol. Chem., 1976, 251(16), 5007-5014.
5. Agnati, L. F.; Fuxe, K.; Zoli, M.; Rondanini, C.; Ogren, S. O. New vistas on synaptic plasticity: the receptor mosaic hypothesis of the engram. Med. Biol., 1982, 60(4), 183-190.
6. Wertman, J.; Dupre, D. J. G protein-coupled receptor dimers: look like their parents, but act like teenagers! J. Recept. Signal. Transduct. Res., 2013, 33(3), 135-138.
7. Zhang, X.; Liu, J.; Jiang, D. Why is dimerization essential for class-C GPCR function? New insights from mGluR1 crystal structure analysis. Protein & Cell, 2014, 5(7), 492-5.
8. Granier, S.; Kobilka, B. A new era of GPCR structural and chemical biology. Nat. Chem. Biol., 2012, 8(8), 670-673.
9. Moreira, I. S. Structural features of the G-protein/GPCR interactions. Biochim. Biophys. Acta., 2014, 1840(1), 16-33.
10. Salom, D.; Padayatti, P. S.; Palczewski, K. Crystallization of G protein-coupled receptors. Methods Cell Biol., 2013, 117(451-468).
11. Ferre, S.; Casado, V.; Devi, L. A.; Filizola, M.; Jockers, R.; Lohse, M. J.; Milligan, G.; Pin, J. P.; Guitart, X. G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives. Pharmacol. Rev., 2014, 66(2), 413-434.
12. Congreve, M.; Langmead, C.; Marshall, F. H. The use of GPCR structures in drug design. Adv. Pharmacol., 2011, 62(1-36).
13. Franco, R.; Martinez-Pinilla, E.; Ricobaraza, A.; McCormick, P. J.; Jesus Giraldo and Francisco, C. In Progress in Molecular Biology and Translational Science; Giraldo, J.; Francisco, C, Eds.; Academic Press, 2013, p 143-162.
14. Fotiadis, D.; Liang, Y.; Filipek, S.; Saperstein, D. A.; Engel, A.; Palczewski, K. Atomic-force microscopy: Rhodopsin dimers in native disc membranes. Nature, 2003, 421(6919), 127-128.
15. Fotiadis, D.; Liang, Y.; Filipek, S.; Saperstein, D. A.; Engel, A.; Palczewski, K. The G protein-coupled receptor rhodopsin in the native membrane. FEBS Lett., 2004, 564(3), 281-288.
16. Suda, K.; Filipek, S.; Palczewski, K.; Engel, A.; Fotiadis, D. The supramolecular structure of the GPCR rhodopsin in solution and native disc membranes. Mol. Membr. Biol., 2004, 21(6), 435-446.
17. Wu, H.; Wang, C.; Gregory, K. J.; Han, G. W.; Cho, H. P.; Xia, Y.; Niswender, C. M.; Katritch, V.; Meiler, J.; Cherezov, V.; Conn, P. J.; Stevens, R. C. Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science, 2014, 344(6179), 58-64.
18. Zhu, L.; Zhao, Q.; Wu, B. Structure-based studies of chemokine receptors. Curr. Opin. Struct. Bio., 2013, 23(4), 539-546.
19. Canals, M.; Burgueno, J.; Marcellino, D.; Cabello, N.; Canela, E. I.; Mallol, J.; Agnati, L.; Ferre, S.; Bouvier, M.; Fuxe, K.; Ciruela, F.; Lluis, C.; Franco, R. Homodimerization of adenosine A2A receptors: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J. Neurochem., 2004, 88(3), 726-734.
20. Lee, S. P.; O'Dowd, B. F.; Rajaram, R. D.; Nguyen, T.; George, S. R. D2 dopamine receptor homodimerization is mediated by multiple sites of interaction, including an intermolecular interaction involving transmembrane domain 4. Biochemistry, 2003, 42(37), 11023-11031.
21. Prinster, S. C.; Hague, C.; Hall, R. A. Heterodimerization of g protein-coupled receptors: specificity and functional significance. Pharmacol. Rev., 2005, 57(3), 289-298.
22. Marshall, F. H.; Jones, K. A.; Kaupmann, K.; Bettler, B. GABAB receptors -the first 7TM heterodimers. Trends. Pharmacol. Sci., 1999, 20(10), 396-399.
23. Nelson, G.; Hoon, M. A.; Chandrashekar, J.; Zhang, Y.; Ryba, N. J.; Zuker, C. S. Mammalian sweet taste receptors. Cell, 2001, 106(3), 381-390.
24. Rocheville, M.; Lange, D. C.; Kumar, U.; Sasi, R.; Patel, R. C.; Patel, Y. C. Subtypes of the somatostatin receptor assemble as functional homo-and heterodimers. J. Biol. Chem., 2000, 275(11), 7862-7869.
25. Rodríguez-Frade, J. M.; del Real, G.; Serrano, A.; Hernanz-Falcón, P.; Soriano, S. F.; Vila-Coro, A. J.; de Ana, A. M.; Lucas, P.; Prieto, I.; Martínez, A. C.; Mellado, M. Blocking HIV-1 infection via CCR5 and CXCR4 receptors by acting in trans on the CCR2 chemokine receptor. Embo J., 2004, 23(1), 66-76.
26. Vilardaga, J. P.; Agnati, L. F.; Fuxe, K.; Ciruela, F. G-proteincoupled receptor heteromer dynamics. J. Cell Sci., 2010, 123(Pt 24), 4215-4220.
27. Chabre, M.; le Maire, M. Monomeric G-protein-coupled receptor as a functional unit. Biochemistry, 2005, 44(27), 9395-9403.
28. Busnelli, M.; Mauri, M.; Parenti, M.; Chini, B. Analysis of GPCR dimerization using acceptor photobleaching resonance energy transfer techniques. Methods Enzymol, 2013, 521,311-327.
29. Hebert, T. E.; Loisel, T. P.; Adam, L.; Ethier, N.; Onge, S. S.; Bouvier, M. Functional rescue of a constitutively desensitized beta2AR through receptor dimerization. Biochem. J., 1998, 330 (Pt 1)(287-293).
30. Hebert, T. E.; Moffett, S.; Morello, J. P.; Loisel, T. P.; Bichet, D. G.; Barret, C.; Bouvier, M. A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J. Biol. Chem., 1996, 271(27), 16384-16392.
31. Park, P. S.; Wells, J. W. Oligomeric potential of the M2 muscarinic cholinergic receptor. J. Neurochem., 2004, 90(3), 537-548.
32. Milligan, G. G-protein-coupled receptor heterodimers: pharmacology, function and relevance to drug discovery. Drug Discov. Today, 2006, 11(11-12), 541-549.
33. Milligan, G.; Bouvier, M. Methods to monitor the quaternary structure of G protein-coupled receptors. FEBS J., 2005, 272(12), 2914-2925.
34. Mizuno, N.; Suzuki, T.; Kishimoto, Y.; Hirasawa, N. Biochemical assay of G protein-coupled receptor oligomerization: adenosine A1 and thromboxane A2 receptors form the novel functional heterooligomer. Methods Cell Biol., 2013, 117(213-227).
35. Raicu, V.; Singh, D. R. FRET spectrometry: a new tool for the determination of protein quaternary structure in living cells. Biophys. J., 2013, 105(9), 1937-1945.
36. Shimomura, O.; Johnson, F. H.; Saiga, Y. Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea. J. Cell Comp. Physiol., 1962, 59(223-239).
37. Morise, H.; Shimomura, O.; Johnson, F. H.; Winant, J. Intermolecular energy transfer in the bioluminescent system of Aequorea. Biochemistry, 1974, 13(12), 2656-2662.
38. Prendergast, F. G.; Mann, K. G. Chemical and physical properties of aequorin and the green fluorescent protein isolated from Aequorea forskalea. Biochemistry, 1978, 17(17), 3448-3453.
39. Chudakov, D. M.; Lukyanov, S.; Lukyanov, K. A. Fluorescent proteins as a toolkit for in vivo imaging. Trends Biotechnol., 2005, 23(12), 605-613.
40. Overton, M. C.; Blumer, K. J. G-protein-coupled receptors function as oligomers in vivo. Curr. Biol., 2000, 10(6), 341-344
41. Kirber, M. T.; Chen, K.; Keaney, J. F. Jr. YFP photoconversion revisited: confirmation of the CFP-like species. Nat. Methods, 2007, 4(10), 767-768.
42. Ward, R. J.; Milligan, G. Structural and biophysical characterisation of G protein-coupled receptor ligand binding using resonance energy transfer and fluorescent labelling techniques. Biochim. Biophys. Acta., 2014, 1838(1 Pt A), 3-14.
43. Kaczor, A. A.; Selent, J. Oligomerization of G protein-coupled receptors: biochemical and biophysical methods. Curr. Med. Chem., 2011, 18(30), 4606-4634.
44. Kaczor, A. A.; Makarska-Bialokoz, M.; Selent, J.; de la Fuente, R. A.; Marti-Solano, M.; Castro, M. Application of BRET for Studying G Protein-Coupled Receptors. Mini Rev. Med. Chem., 2014, 14(5), 411-425.
45. Ciruela, F.; Vilardaga, J. P.; Fernandez-Duenas, V. Lighting up multiprotein complexes: lessons from GPCR oligomerization. Trends Biotechnol., 2010, 28(8), 407-415.
46. Porrello, E. R.; Pfleger, K. D.; Seeber, R. M.; Qian, H.; Oro, C.; Abogadie, F.; Delbridge, L. M.; Thomas, W. G. Heteromerization of angiotensin receptors changes trafficking and arrestin recruitment profiles. Cell Signal., 2011, 23(11), 1767-1776.
47. Kerppola, T. K. Design and implementation of bimolecular fluorescence complementation (BiFC) assays for the visualization of protein interactions in living cells. Nat. Protoc., 2006, 1(3), 1278-1286.
48. Maggio, R.; Rocchi, C.; Scarselli, M. Experimental strategies for studying G protein-coupled receptor homo-and heteromerization with radioligand binding and signal transduction methods. Methods Enzymol., 2013, 521(295-310).
49. Goupil, E.; Laporte, S. A.; Hebert, T. E. A simple method to detect allostery in GPCR dimers. Methods Cell Biol., 2013, 117(165-179).
50. Suzuki, K. G.; Kasai, R. S.; Fujiwara, T. K.; Kusumi, A. Singlemolecule imaging of receptor-receptor interactions. Methods Cell Biol., 2013, 117(373-390).
51. Castillo-Badillo, J. A.; Cabrera-Wrooman, A.; Garcia-Sainz, J. A. Visualizing G Protein-coupled Receptors in Action through Confocal Microscopy Techniques. Arch. Med. Res., 2014, 45(4), 283-293.
52. Lebon, G.; Warne, T.; Edwards, P. C.; Bennett, K.; Langmead, C. J.; Leslie, A. G.; Tate, C. G. Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature, 2012, 474(7352), 521-525.
53. Schertler, G. F. Structure of rhodopsin. Eye (Lond), 1998, 12 (Pt 3b)(504-510).
54. Palczewski, K.; Kumasaka, T.; Hori, T.; Behnke, C. A.; Motoshima, H.; Fox, B. A.; Le Trong, I.; Teller, D. C.; Okada, T.; Stenkamp, R. E.; Yamamoto, M.; Miyano, M. Crystal structure of rhodopsin: A G protein-coupled receptor. Science, 2000, 289(5480), 739-745.
55. Rasmussen, S. G.; Choi, H. J.; Rosenbaum, D. M.; Kobilka, T. S.; Thian, F. S.; Edwards, P. C.; Burghammer, M.; Ratnala, V. R.; Sanishvili, R.; Fischetti, R. F.; Schertler, G. F.; Weis, W. I.; Kobilka, B. K. Crystal structure of the human beta2 adrenergic Gprotein-coupled receptor. Nature, 2007, 450(7168), 383-387.
56. Wu, B.; Chien, E. Y.; Mol, C. D.; Fenalti, G.; Liu, W.; Katritch, V.; Abagyan, R.; Brooun, A.; Wells, P.; Bi, F. C.; Hamel, D. J.; Kuhn, P.; Handel, T. M.; Cherezov, V.; Stevens, R. C. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science, 2010, 330(6007), 1066-1071.
57. Crump, M. P.; Gong, J. H.; Loetscher, P.; Rajarathnam, K.; Amara, A.; Arenzana-Seisdedos, F.; Virelizier, J. L.; Baggiolini, M.; Sykes, B. D.; Clark-Lewis, I. Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1. Embo J., 1997, 16(23), 6996-7007.
58. Stephens, B.; Handel, T. M. Chemokine receptor oligomerization and allostery. Prog. Mol. Biol. Transl. Sci., 2013, 115(375-420).
59. Baggiolini, M. Chemokines and leukocyte traffic. Nature, 1998, 392(6676), 565-568.
60. Prasanna, X.; Chattopadhyay, A.; Sengupta, D. Cholesterol modulates the dimer interface of the beta(2)-adrenergic receptor via cholesterol occupancy sites. Biophys J., 2014, 106(6), 1290-1300.
61. Hanson, M. A.; Cherezov, V.; Griffith, M. T.; Roth, C. B.; Jaakola, V. P.; Chien, E. Y.; Velasquez, J.; Kuhn, P.; Stevens, R. C. A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure, 2008, 16(6), 897-905.
62. Wang, C. I.; Lewis, R. J. Emerging opportunities for allosteric modulation of G-protein coupled receptors. Biochem. Pharma., 2013, 85(2), 153-162.
63. Satoh, A.; Nagatomi, Y.; Hirata, Y.; Ito, S.; Suzuki, G.; Kimura, T.; Maehara, S.; Hikichi, H.; Satow, A.; Hata, M.; Ohta, H.; Kawamoto, H. Discovery and in vitro and in vivo profiles of 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-Nmethylbenzam ide as novel class of an orally active metabotropic glutamate receptor 1 (mGluR1) antagonist. Bioorg. Med. Chem. Lett., 2009, 19(18), 5464-5468.
64. Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.; Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. UCSF Chimera--a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
65. Kaczor, A. A.; Selent, J.; Poso, A. Structure-based molecular modeling approaches to GPCR oligomerization. Methods. Cell. Biol., 2013, 117(91-104).
66. Strasser, A.; Wittmann, H. J. Molecular modeling studies give hint for the existence of a symmetric hbeta(2)R-Galphabetagammahomodimer. J. Mol. Model., 2013, 19(10), 4443-4457.
67. Ghosh, A.; Sonavane, U.; Joshi, R. Multiscale modelling to understand the self-assembly mechanism of human beta2-adrenergic receptor in lipid bilayer. Comput. Biol. Chem., 2014, 48(29-39).
68. Mondal, S.; Johnston, J. M.; Wang, H.; Khelashvili, G.; Filizola, M.; Weinstein, H. Membrane driven spatial organization of GPCRs. Sci. Rep., 2013, 3(2909).
69. Milligan, G. G protein-coupled receptor dimerization: function and ligand pharmacology. Mol. Pharmacol., 2004, 66(1), 1-7.
70. Dalrymple, M. B.; Pfleger, K. D. G.; Eidne, K. A. G proteincoupled receptor dimers: Functional consequences, disease states and drug targets. Pharma. Ther., 2008, 118(3), 359-371.
71. Gomes, I.; Fujita, W.; Chandrakala, M. V.; Devi, L. A.; Jesus Giraldo and Francisco, C. In Progress in Molecular Biology and Translational Science; Jesus Giraldo and Francisco, C., Ed.; Academic Press, 2013, p 207-265.
72. AbdAlla, S.; Abdel-Baset, A.; Lother, H.; el Massiery, A.; Quitterer, U. Mesangial AT1/B2 receptor heterodimers contribute to angiotensin II hyperresponsiveness in experimental hypertension. J. Mol. Neurosci., 2005, 26(2-3), 185-192.
73. AbdAlla, S.; Lother, H.; el Massiery, A.; Quitterer, U. Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat. Med., 2001, 7(9), 1003-1009.
74. AbdAlla, S.; Lother, H.; Quitterer, U. AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration. Nature, 2000, 407(6800), 94-98.
75. Hernanz-Falcon, P.; Rodriguez-Frade, J. M.; Serrano, A.; Juan, D.; del Sol, A.; Soriano, S. F.; Roncal, F.; Gomez, L.; Valencia, A.; Martinez, A. C.; Mellado, M. Identification of amino acid residues crucial for chemokine receptor dimerization. Nat. Immunol., 2004, 5(2), 216-223.
76. Mellado, M.; Martinez, A. C.; Rodriguez-Frade, J. M. Analysis of G-protein-coupled receptor dimerization following chemokine signaling. Methods, 2002, 27(4), 349-357.
77. Mellado, M.; Rodriguez-Frade, J. M.; Vila-Coro, A. J.; Fernandez, S.; Martin de Ana, A.; Jones, D. R.; Toran, J. L.; Martinez, A. C. Chemokine receptor homo-or heterodimerization activates distinct signaling pathways. Embo J., 2001, 20(10), 2497-2507.
78. Mellado, M.; Vila-Coro, A. J.; Martinez, C.; Rodriguez-Frade, J. M. Receptor dimerization: a key step in chemokine signaling. Cell. Mol. Biol. (Noisy-le-grand), 2001, 47(4), 575-582.
79. Vila-Coro, A. J.; Rodríguez-Frade, J. M.; Martin De Ana, A.; Moreno-Ortiz, M. C.; Martínez, A. C.; Mellado, M. The chemokine SDF-1alpha triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway. FASEB J., 1999, 13(13), 1699-1710.
80. Petaja-Repo, U. E.; Hogue, M.; Laperriere, A.; Walker, P.; Bouvier, M. Export from the endoplasmic reticulum represents the limiting step in the maturation and cell surface expression of the human delta opioid receptor. J. Biol. Chem., 2000, 275(18), 13727-13736.
81. Kammerer, R. A.; Frank, S.; Schulthess, T.; Landwehr, R.; Lustig, A.; Engel, J. Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices. Biochemistry, 1999, 38(40), 13263-13269.
82. White, J. H.; Wise, A.; Main, M. J.; Green, A.; Fraser, N. J.; Disney, G. H.; Barnes, A. A.; Emson, P.; Foord, S. M.; Marshall, F. H. Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature, 1998, 396(6712), 679-682.
83. Kuner, R.; Kohr, G.; Grunewald, S.; Eisenhardt, G.; Bach, A.; Kornau, H. C. Role of heteromer formation in GABAB receptor function. Science, 1999, 283(5398), 74-77.
84. Issafras, H.; Angers, S.; Bulenger, S.; Blanpain, C.; Parmentier, M.; Labbe-Jullie, C.; Bouvier, M.; Marullo, S. Constitutive agonistindependent CCR5 oligomerization and antibody-mediated clustering occurring at physiological levels of receptors. J. Biol. Chem., 2002, 277(38), 34666-34673.
85. El-Asmar, L.; Springael, J. Y.; Ballet, S.; Andrieu, E. U.; Vassart, G.; Parmentier, M. Evidence for negative binding cooperativity within CCR5-CCR2b heterodimers. Mol. Pharm., 2005, 67(2), 460-469.
86. Scholten, D. J.; Canals, M.; Maussang, D.; Roumen, L.; Smit, M. J.; Wijtmans, M.; de Graaf, C.; Vischer, H. F.; Leurs, R. Pharmacological modulation of chemokine receptor function. Br. J. Pharma., 2012, 165(6), 1617-1643.
87. Berger, E. A.; Murphy, P. M.; Farber, J. M. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev. Immunol., 1999, 17(657-700).
88. Ridderstad Wollberg, A.; Ericsson-Dahlstrand, A.; Jureus, A.; Ekerot, P.; Simon, S.; Nilsson, M.; Wiklund, S. J.; Berg, A. L.; Ferm, M.; Sunnemark, D.; Johansson, R. Pharmacological inhibition of the chemokine receptor CX3CR1 attenuates disease in a chronic-relapsing rat model for multiple sclerosis. Proc. Natl. Acad Sci. U S A., 2014, 111(14), 5409-5414.
89. Tak, P. P.; Balanescu, A.; Tseluyko, V.; Bojin, S.; Drescher, E.; Dairaghi, D.; Miao, S.; Marchesin, V.; Jaen, J.; Schall, T. J.; Bekker, P. Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis: CARAT-2, a randomised, placebo controlled clinical trial. Ann. Rheum. Dis., 2012, 72(3), 337-344.
90. Wu, X.; Lee, V. C.; Chevalier, E.; Hwang, S. T. Chemokine receptors as targets for cancer therapy. Curr. Pharm. Des., 2009, 15(7), 742-757.
91. Griffith, J. W.; Sokol, C. L.; Luster, A. D. Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu. Rev. Immunol., 2014, 32(659-702).
92. Christopoulos, A.; Kenakin, T. G protein-coupled receptor allosterism and complexing. Pharmacol. Rev., 2002, 54(2), 323-374.
93. Proudfoot, A. E.; Power, C. A.; Schwarz, M. K. Anti-chemokine small molecule drugs: a promising future? Expert Opin. Investig. Drugs, 2010, 19(3), 345-355.
94. Watson, C.; Jenkinson, S.; Kazmierski, W.; Kenakin, T. The CCR5 receptor-based mechanism of action of 873140, a potent allosteric noncompetitive HIV entry inhibitor. Mol. Pharmal., 2005, 67(4), 1268-1282.
95. Gerlach, L. O.; Skerlj, R. T.; Bridger, G. J.; Schwartz, T. W. Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J. Biol. Chem., 2001, 276(17), 14153-14160.
96. Kim, S. Y.; Lee, C. H.; Midura, B. V.; Yeung, C.; Mendoza, A.; Hong, S. H.; Ren, L.; Wong, D.; Korz, W.; Merzouk, A.; Salari, H.; Zhang, H.; Hwang, S. T.; Khanna, C.; Helman, L. J. Inhibition of the CXCR4/CXCL12 chemokine pathway reduces the development of murine pulmonary metastases. Clin. Exp. Metast., 2008, 25(3), 201-211.
97. Wong, D.; Korz, W. Translating an Antagonist of Chemokine Receptor CXCR4: from bench to bedside. Clin. Cancer Res., 2008, 14(24), 7975-7980.
98. Baeck, C.; Wehr, A.; Karlmark, K. R.; Heymann, F.; Vucur, M.; Gassler, N.; Huss, S.; Klussmann, S.; Eulberg, D.; Luedde, T.; Trautwein, C.; Tacke, F. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut., 2012, 61(3), 416-426.
99. Ling, M. F.; Luster, A. D. Novel approach to inhibiting chemokine function. EMBO Mol. Med., 2011, 3(9), 510-512.
100. Kim, M. Y.; Byeon, C. W.; Hong, K. H.; Han, K. H.; Jeong, S. Inhibition of the angiogenesis by the MCP-1 (monocyte chemoattractant protein-1) binding peptide. FEBS Lett., 2005, 579(7), 1597-1601.
101. Tamamis, P.; Floudas, C. A. Molecular Recognition of CCR5 by an HIV-1 gp120 V3 Loop. PLoS One, 2014, 9(4), e95767.
102. Mahad, D.; Callahan, M. K.; Williams, K. A.; Ubogu, E. E.; Kivisakk, P.; Tucky, B.; Kidd, G.; Kingsbury, G. A.; Chang, A.; Fox, R. J.; Mack, M.; Sniderman, M. B.; Ravid, R.; Staugaitis, S. M.; Stins, M. F.; Ransohoff, R. M. Modulating CCR2 and CCL2 at the blood-brain barrier: relevance for multiple sclerosis pathogenesis. Brain, 2006, 129(Pt 1), 212-223.
103. Mahad, D. J.; Ransohoff, R. M. The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Semin. Immunol., 2003, 15(1), 23-32.
104. Hiller, C.; Kuhhorn, J.; Gmeiner, P. Class A G-protein-coupled receptor (GPCR) dimers and bivalent ligands. J. Med. Chem., 2013, 56(17), 6542-6559.
105. Tanaka, T.; Nomura, W.; Narumi, T.; Masuda, A.; Tamamura, H. Bivalent ligands of CXCR4 with rigid linkers for elucidation of the dimerization state in cells. J. Am. Chem. Soc., 2010, 132(45), 15899-15901.
106. Vila-Coro, A. J.; Mellado, M.; Martin de Ana, A.; Lucas, P.; del Real, G.; Martínez, A. C.; Rodríguez-Frade, J. M. HIV-1 infection through the CCR5 receptor is blocked by receptor dimerization. Proc Natl Acad Sci U S A., 2000, 97(7), 3388-3393.
107. Ruff, M. R.; Melendez-Guerrero, L. M.; Yang, Q. E.; Ho, W. Z.; Mikovits, J. W.; Pert, C. B.; Ruscetti, F. A. Peptide T inhibits HIV-1 infection mediated by the chemokine receptor-5 (CCR5). Antiviral Res., 2001, 52(1), 63-75.
108. Lear, J. D.; Wasserman, Z. R.; DeGrado, W. F. Synthetic amphiphilic peptide models for protein ion channels. Science, 1988, 240(4856), 1177-1181.
109. Klein, M.A. Stabilized Helical Peptides: A Strategy to Target Protein-Protein Interactions. ACS Med. Chem. Lett., 2014, 5(8), 838-9.
110. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug. Deliv. Rev., 2001, 46(1-3), 3-26.
111. Haridas, V. From Peptides to Non-Peptide Alpha-Helix Inducers and Mimetics. Eur. J. Org. Chem., 2009, 2009(30), 5112-5128.
112. Jayatunga, M. K. P.; Thompson, S.; Hamilton, A. D. Helix mimetics: Outwards and upwards. Bioorg. Med. Chem. Lett., 2014, 24(3), 717-724.
113. Gilon, C.; Lohof, E.; Friedler, A.; Kessler, H. Synthesis of Cyclic Peptides. in Houben-Weyl: Methods of Organic Chemistry (Goodman, M., Felix, A., Moroder, L., and Toniolo, C., Eds.), 2003, E 22b, Synthesis of Peptides and Peptidomimetics,(461-542), Thieme Verlag, Stuttgart, Germany.
114. Merrifield, R. B. Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. J. Am. Chem. Soc., 1963, 85(14), 2149-2154.
115. Shepherd, N. E.; Hoang, H. N.; Abbenante, G.; Fairlie, D. P. Single turn peptide alpha helices with exceptional stability in water. J. Am. Chem. Soc., 2005, 127(9), 2974-2983.
116. Yang, B.; Liu, D.; Huang, Z. Synthesis and helical structure of lactam bridged BH3 peptides derived from pro-apoptotic Bcl-2 family proteins. Bioorg. Med. Chem. Lett., 2004, 14(6), 1403-1406.
117. Doig, A. J. Stability and design of alpha-helical peptides. Prog. Mol. Biol. Transl. Sci., 2008, 83(1-52).
118. Henchey, L. K.; Jochim, A. L.; Arora, P. S. Contemporary strategies for the stabilization of peptides in the alpha-helical conformation. Curr. Opin. Chem. Biol., 2008, 12(6), 692-697.
119. du Vigneaud, V.; Ressler, C.; Swan, J. M.; Roberts, C. W.; Katsoyannis, P. G. The Synthesis of Oxytocin1. J. Am. Chem. Soc., 1954, 76(12), 3115-3121.
120. Leduc, A. M.; Trent, J. O.; Wittliff, J. L.; Bramlett, K. S.; Briggs, S. L.; Chirgadze, N. Y.; Wang, Y.; Burris, T. P.; Spatola, A. F. Helix-stabilized cyclic peptides as selective inhibitors of steroid receptor-coactivator interactions. Proc. Natl. Acad. Sci., USA, 2003, 100(20), 11273-11278.
121. Garner, J.; Harding, M. M. Design and synthesis of alpha-helical peptides and mimetics. Org. Biomol. Chem., 2007, 5(22), 3577-3585.
122. Jackson, D. Y.; King, D. S.; Chmielewski, J.; Singh, S.; Schultz, P. G. General-Approach to the Synthesis of Short Alpha-Helical Peptides. J. Am. Chem. Soc., 1991, 113(24), 9391-9392.
123. Pease, J. H.; Storrs, R. W.; Wemmer, D. E. Folding and activity of hybrid sequence, disulfide-stabilized peptides. Proc. Natl. Acad. Sci. U. S. A., 1990, 87(15), 5643-5647.
124. Pellegrini, M.; Royo, M.; Chorev, M.; Mierke, D. F. Conformational consequences of i,i+3 cystine linkages: Nucleation for alphahelicity? J. Pept. Res., 1997, 49(5), 404-414
125. Taylor, J. W. The synthesis and study of side-chain lactam-bridged peptides. Biopolymers, 2002, 66(1), 49-75.
126. Calvo, J. C.; Choconta, K. C.; Diaz, D.; Orozco, O.; Bravo, M. M.; Espejo, F.; Salazar, L. M.; Guzman, F.; Patarroyo, M. E. An alpha helix conformationally restricted peptide is recognized by cervical carcinoma patients' sera. J. Med. Chem., 2003, 46(25), 5389-5394.
127. Cabezas, E.; Satterthwait, A. C. The Hydrogen Bond Mimic Approach: Solid-Phase Synthesis of a Peptide Stabilized as an _-Helix with a Hydrazone Link. J. Am. Chem. Soc., 1999, 121(16), 3862-3875.
128. Blackwell, H. E.; Sadowsky, J. D.; Howard, R. J.; Sampson, J. N.; Chao, J. A.; Steinmetz, W. E.; O'Leary, D. J.; Grubbs, R. H. Ringclosing metathesis of olefinic peptides: Design, synthesis, and structural characterization of macrocyclic helical peptides. J. Org. Chem., 2001, 66(16), 5291-5302.
129. Patgiri, A.; Menzenski, M. Z.; Mahon, A. B.; Arora, P. S. Solidphase synthesis of short alpha-helices stabilized by the hydrogen bond surrogate approach. Nat. Protoc., 2010, 5(11), 1857-1865.
130. Patgiri, A.; Yadav, K. K.; Arora, P. S.; Bar-Sagi, D. An orthosteric inhibitor of the Ras-Sos interaction. Nat. Chem. Biol., 2011, 7(9), 585-587.
131. Kim, Y. W.; Grossmann, T. N.; Verdine, G. L. Synthesis of allhydrocarbon stapled alpha-helical peptides by ring-closing olefin metathesis. Nat. Protoc., 2011, 6(6), 761-771.
132. Verdine, G. L.; Hilinski, G. J. Stapled Peptides for Intracellular Drug Targets. Method. Enzymol., 2012, 503(3-33).
133. Walensky, L. D.; Kung, A. L.; Escher, I.; Malia, T. J.; Barbuto, S.; Wright, R. D.; Wagner, G.; Verdine, G. L.; Korsmeyer, S. J. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science, 2004, 305(5689), 1466-1470.
134. Rodríguez-Frade, J. M.; Vila-Coro, A. J.; de Ana, A. M.; Albar, J. P.; Martínez, A. C.; Mellado, M. The chemokine monocyte chemoattractant protein-1 induces functional responses through dimerization of its receptor CCR2. Proc. Natl. Acad. Sci. U. S. A., 1999, 96(7), 3628-3633.
135. Hurevich, M.; Ratner-Hurevich, M.; Tal-Gan, Y.; Shalev, D. E.; Ben-Sasson, S. Z.; Gilon, C. Backbone cyclic helix mimetic of chemokine (C-C motif) receptor 2: a rational approach for inhibiting dimerization of G protein-coupled receptors. Bioorg. Med. Chem., 2013, 21(13), 3958-3966.
136. Hurevich, M.; Barda, Y.; Gilon, C. Synthesis of novel urea bridged macrocyclic molecules using BTC. Heterocycles, 2007, 73(1), 617-625.
137. Hurevich, M.; Tal-Gan, Y.; Klein, S.; Barda, Y.; Levitzki, A.; Gilon, C. Novel method for the synthesis of urea backbone cyclic peptides using new Alloc-protected glycine building units. J. Pept. Sci., 2010, 16(4), 178-185.
138. Hayouka, Z.; Hurevich, M.; Levin, A.; Benyamini, H.; Iosub, A.; Maes, M.; Shalev, D. E.; Loyter, A.; Gilon, C.; Friedler, A. Cyclic peptide inhibitors of HIV-1 integrase derived from the LEDGF/p75 protein. Bioorg. Med. Chem., 2010, 18(23), 8388-8395.
139. Hess, S.; Linde, Y.; Ovadia, O.; Safrai, E.; Shalev, D. E.; Swed, A.; Halbfinger, E.; Lapidot, T.; Winkler, I.; Gabinet, Y.; Faier, A.; Yarden, D.; Xiang, Z.; Portillo, F. P.; Haskell-Luevano, C.; Gilon, C.; Hoffman, A. Backbone cyclic peptidomimetic melanocortin-4 receptor agonist as a novel orally administrated drug lead for treating obesity. J. Med. Chem., 2008, 51(4), 1026-1034.
140. Gazal, S.; Gelerman, G.; Ziv, O.; Karpov, O.; Litman, P.; Bracha, M.; Afargan, M.; Gilon, C. Human somatostatin receptor specificity of backbone-cyclic analogues containing novel sulfur building units. J. Med. Chem., 2002, 45(8), 1665-1671.
141. Cummings, C. G.; Hamilton, A. D. Disrupting protein-protein interactions with non-peptidic, small molecule alpha-helix mimetics. Curr. Opin. Chem. Biol., 2010, 14(3), 341-346.
142. Perato, S.; Fogha, J.; Sebban, M.; Voisin-Chiret, A. S.; Sopkova-de Oliveira Santos, J.; Oulyadi, H.; Rault, S. Conformation control of abiotic alpha-helical foldamers. J. Chem. Inf. Model, 2013, 53(10), 2671-2680.
143. Munoz, L. M.; Holgado, B. L.; Martinez, A. C.; Rodriguez-Frade, J. M.; Mellado, M. Chemokine receptor oligomerization: a further step toward chemokine function. Immunol. Lett., 2012, 145(1-2), 23-29.
144. Toth, P. T.; Ren, D.; Miller, R. J. Regulation of CXCR4 receptor dimerization by the chemokine SDF-1alpha and the HIV-1 coat protein gp120: a fluorescence resonance energy transfer (FRET) study. J. Pharmacol. Exp. Ther., 2004, 310(1), 8-17.
145. Babcock, G. J.; Farzan, M.; Sodroski, J. Ligand-independent dimerization of CXCR4, a principal HIV-1 coreceptor. J. Biol. Chem., 2003, 278(5), 3378-3385.
146. Hamatake, M.; Aoki, T.; Futahashi, Y.; Urano, E.; Yamamoto, N.; Komano, J. Ligand-independent higher-order multimerization of CXCR4, a G-protein-coupled chemokine receptor involved in targeted metastasis. Cancer Sci., 2009, 100(1), 95-102.
147. Dorsch, S.; Klotz, K. N.; Engelhardt, S.; Lohse, M. J.; Bunemann, M. Analysis of receptor oligomerization by FRAP microscopy. Nat. Methods, 2009, 6(3), 225-230.
148. Fonseca, J. M.; Lambert, N. A. Instability of a class a G proteincoupled receptor o ligomer interface. Mol. Pharmacol., 2009, 75(6), 1296-1299.
149. Hern, J. A.; Baig, A. H.; Mashanov, G. I.; Birdsall, B.; Corrie, J. E.; Lazareno, S.; Molloy, J. E.; Birdsall, N. J. Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules. PNAS, 2010, 107(6), 2693-2698.
150. Sohy, D.; Parmentier, M.; Springael, J. Y. Allosteric transinhibition by specific antagonists in CCR2/CXCR4 heterodimers. J. Biol. Chem., 2007, 282(41), 30062-30069.
151. Sohy, D.; Yano, H.; de Nadai, P.; Urizar, E.; Guillabert, A.; Javitch, J. A.; Parmentier, M.; Springael, J. Y. Heterooligomerization of CCR2, CCR5, and CXCR4 and the protean effects of "selective" antagonists. J. Biol. Chem., 2009, 284(45), 31270-31279.
152. Borroto-Escuela, D. O.; Brito, I.; Romero-Fernandez, W.; Di Palma, M.; Oflijan, J.; Skieterska, K.; Duchou, J.; Van Craenenbroeck, K.; Suarez-Boomgaard, D.; Rivera, A.; Guidolin, D.; Agnati, L. F.; Fuxe, K. The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components. Int. J. Mol. Sci., 2014, 15(5), 8570-8590.
153. Fuxe, K.; Borroto-Escuela, D. O.; Romero-Fernandez, W.; Palkovits, M.; Tarakanov, A. O.; Ciruela, F.; Agnati,; L. F. Moonlighting proteins and protein-protein interactions as neurotherapeutic targets in the g protein-coupled receptor field. Neuropsychopharmacology, 2014, 39(1), 131-155.
154. Lalonde, S.; Sero, A.; Pratelli, R.; Pilot, G.; Chen, J.; Sardi, M. I.; Parsa, S. A.; Kim, D. Y.; Acharya, B. R.; Stein, E. V.; Hu, H. C.; Villiers, F.; Takeda, K.; Yang, Y.; Han, Y. S.; Schwacke, R.; Chiang, W.; Kato, N.; Loque, D.; Assmann, S. M.; Kwak, J. M.; Schroeder, J. I.; Rhee, S. Y.; Frommer, W. B. A membrane protein/ signaling protein interaction network for Arabidopsis version AMPv2. Front. Physiol., 2010, 1(24).
155. Obrdlik, P.; El-Bakkoury, M.; Hamacher, T.; Cappellaro, C.; Vilarino, C.; Fleischer, C.; Ellerbrok, H.; Kamuzinzi, R.; Ledent, V.; Blaudez, D.; Sanders, D.; Revuelta, J. L.; Boles, E.; Andre, B.; Frommer, W. B. K+ channel interactions detected by a genetic system optimized for systematic studies of membrane protein interactions. Proc. Natl. Acad Sci. U S A., 2004, 101(33), 12242-12247.
156. Jones, A. M.; Xuan, Y.; Xu, M.; Wang, R. S.; Ho, C. H.; Lalonde, S.; You, C. H.; Sardi, M. I.; Parsa, S. A.; Smith-Valle, E.; Su, T.; Frazer, K. A.; Pilot, G.; Pratelli, R.; Grossmann, G.; Acharya, B. R.; Hu, H. C.; Engineer, C.; Villiers, F.; Ju, C.; Takeda, K.; Su, Z.; Dong, Q.; Assmann, S. M.; Chen, J.; Kwak, J. M.; Schroeder, J. I.; Albert, R.; Rhee, S. Y.; Frommer, W. B. Border control--a membrane-linked interactome of Arabidopsis. Science, 2014, 344(6185), 711-716.