Small multivalent architectures mimicking homotrimers of the TNF superfamily member CD40L: Delineating the relationship between structure and effector function

Journal of the American Chemical Society

Volumn 129, Issue 44, 2007, Pages 13480-13492

  Trouche, Nathalie ^a   Wieckowski, Sébastien ^a   Sun, Weimin ^a,b   Chaloin, Olivier ^a   Hoebeke, Johan ^a   Fournel, Sylvie ^a   Guichard, Gilles ^a  

^a INSTITUT DE BIOLOGIE MOLÉCULAIRE ET CELLULAIRE   (France)

^b BEIJING JIAOTONG UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

CELL CULTURE; MOLECULAR STRUCTURE; PATHOGENS; TUMORS;

CENTRAL SCAFFOLD; MULTIVALENT ARCHITECTURES MIMICKING HOMOTRIMERS; SYNTHETIC MULTIVALENT LIGANDS; TNF SUPERFAMILY;

LIGANDS;

CD40 ANTIGEN; CD40 LIGAND; CELL SURFACE RECEPTOR; RECEPTOR ANTIBODY; SCAFFOLD PROTEIN; TUMOR NECROSIS FACTOR;

ANIMAL CELL; ARTICLE; EFFECTOR CELL; IMMUNITY; LIGAND BINDING; MOLECULAR RECOGNITION; NONHUMAN; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN STRUCTURE; RECEPTOR BINDING; SIGNAL TRANSDUCTION;

ANTIGENS, CD40; BINDING SITES; CD40 LIGAND; LIGANDS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP; TIME FACTORS;

EID: 35948945062     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja073169m     Document Type: Article

References (139)

1. For review, see: (a) Davis, J. M.; Tsou, L. K.; Hamilton, A. D. Chem. Soc. Rev. 2007, 36, 326-334.
2. (b) Zhao, L.; Chmielewski, J. Curr. Opin. Struct. Biol. 2005, 15, 31-34.
3. (c) Yin, H.; Hamilton, A. D. Angew. Chem., Int. Ed. 2005, 44, 4130-4163.
4. (d) Arkin, M. R.; Wells, J. A. Nat. Rev. Drug Discovery 2004, 3, 301-317.
5. (e) Pagliaro, P.; Felding, J.; Audouze, K.; Nielsen, S. J.; Terry, R. B.; Krog-Jensen, C.; Butcher, S. Curr. Opin. Chem. Biol. 2004, 8, 442-449.
6. (f) Berg, T. Angew. Chem., Int. Ed. 2003, 42, 2462-2481;
7. Angew. Chem. 2003, 115, 2566-2586.
8. (g) Toogood, P. L. J. Med. Chem. 2002, 45, 1543-1558.
9. (h) Peczuh, M. W.; Hamilton, A. D. Chem. Rev. 2000, 100, 2749-2494.
10. (i) Cochran, A. G. Chem. Biol. 2000, 7, R85-R94.
11. (a) Lo Conte, L.; Chothia, C.; Janin, J. J. Mol. Biol. 1999, 285, 2177-2198.
12. (b) Chakrabarti, P.; Janin, J. Proteins 2002, 47, 334-343.
13. (a) Austin, D. J.; Crabtree, G. R.; Schreiber, S. L. Chem. Biol. 1994, 1, 131-6.
14. (b) Klemm, J. D.; Crabtree, G. R.; Schreiber, S. L. Annu. Rev. Immunol. 1998, 16, 569-592.
15. (a) Heldin, K.-H. Cell 1995, 80, 214-223.
16. (b) Heldin, C. H.; Ostman, A. Growth Factor Rev. 1996, 7, 3-10.
17. (a) Schlessinger, J. Cell 2000, 103, 211-225.
18. (b) Lemmon, M. A.; Schlessinger, J. Methods Mol. Biol. 1998, 84, 49-71.
19. (a) Germain, R. N. Curr. Biol. 1997, 7, R640-644.
20. (b) Alarcón, B.; Swamy, M.; van Santen, H. M.; Schamel, W. W. A. EMBO J. 2006, 7, 490-495.
21. (a) Ozinsky, A.; Underhill, D. M.; Fontenot, J. D.; Hajjar, A. M.; Smith, K. D.; Wilson, C. B.; Schroeder, L.; Aderem, A. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 13766-13771.
22. (b) Choe, J.; Kelker M. S.; Wilson, I. A. Science 2005, 309, 581-585.
23. (c) Kirk, P.; Bazan, J. Immunity, 2005, 23, 347-350.
24. (a) Bouvier, M. Nat. Rev. Neurosci. 2001, 2, 274-286.
25. (b) George, S. R.; O'Dowd, B. F.; Lee, S. P. Nat. Rev. Drug Discovery 2002, 1, 808-820.
26. (c) Park, P. S.; Filipek, S.; Wells, J. W.; Palczewski, K. Biochemistry 2004, 43, 15643-15656.
27. (d) Prinster, S. C.; Hague, C.; Hall, R. A. Pharmacol. Rev. 2005, 57, 289-298.
28. (e) Bulenger, S.; Marullo, S.; Bouvier, M. Trends Pharmacol. Sci. 2005, 26, 131-137.
29. For early examples of carbohydrate-based multivalent inhibitors (glycopolymers and glycodendrimers) of influenza virus hemagglutinin binding to host cells, see: (a) Spaltenstein, A.; Whitesides, G. M. J. Am. Chem. Soc. 1991, 113, 686-687.
30. (b) Sabesan, S.; Duus, J. O.; Domaille, P.; Kelm, S.; Paulson, J. C. J. Am. Chem. Soc. 1991, 113, 5865-5866.
31. (c) Gamian, A.; Chomik, M.; Laferriere, C. A.; Roy, R. Can. J. Microbiol. 1991, 37, 233-237.
32. (d) Kingery-Wood, J. E.; Williams, K. W.; Sigal, G. B.; Whitesides, G. M. J. Am. Chem. Soc. 1992, 114, 7303-7305.
33. (e) Sparks, M. A.; Williams, K. W.; Whitesides, G. M. J. Med. Chem. 1993, 36, 778-783.
34. (f) Roy, R.; Pon, R. A.; Tropper, F. D.; Andersson, F. O. J. Chem. Soc., Chem. Commun. 1993, 264-265.
35. (g) Roy, R.; Zanini, D.; Meunier, S. J.; Romanowska, A. J. Chem. Soc., Chem. Commun. 1993, 1869-1872.
36. Selected recent examples of multivalent inhibitors: (a) Dimick, S. M.; Powell, S. C.; McMahon, S. A.; Moothoo, D. N.; Naismith, J. H.; Toone, E. J. J. Am. Chem. Soc. 1999, 121, 10286-10296.
37. (b) Kitov, P. I.; Sadowska, J. M.; Mulvey, G.; Armstrong, G. D.; Ling, H.; Pannu, N. S.; Read, R. J.; Bundle, D. R. Nature 2000, 403, 669-672.
38. (c) Merritt, E. A.; Zhang, Z.; Pickens, J. C.; Ahn, M.; Hol, W. G.; Fan, E. J. Am. Chem. Soc. 2002, 124, 8818-8824.
39. (d) Gestwicki, J. E.; Cairo, C. W.; Strong, L. E.; Oetjen, K. A.; Kiessling, L. L. J. Am. Chem. Soc. 2002, 124, 14922-14933;
40. Gradl, S. N.; Felix, J. P.; Isacoff, E. Y.; Garcia, M. L.; Trauner, D. J. Am. Chem. Soc. 2003, 125, 12668-12669.
41. (e) Thumshirn, G.; Hersel, U.; Goodman, S. L.; Kessler, H. Chem. Eur. J. 2003, 9, 2717-2725.
42. (f) Boturyn, D.; Coll, J.-L.; Garanger, E.; Favrot, M.-C.; Dumy, P. J. Am. Chem. Soc. 2004, 126, 5730-5739.
43. (g) Wolfenden, M. L.; Cloninger, M. J. J. Am. Chem. Soc. 2005, 127, 12168-12169.
44. (h) Arosio, D.; Fontanella, M.; Baldini, L.; Mauri, L.; Bernardi, A.; Casnati, A.; Sansone, F.; Ungaro, R. J. Am. Chem. Soc. 2005, 127, 3660-3661.
45. For early examples of bivalent opioid ligands, see: (a) Portoghese, P. S. J. Med. Chem. 2001; 44, 2259-2269.
46. (b) Erez; M.; Takemori, A. E.; Portoghese, P. S. J. Med. Chem. 1982, 25, 847-849; Portoghese, P. S.; Larson, D. L.; Sayre, L. M.; Yim, C. B.
47. (c) Ronsisvalle, G.; Tam, S. W.; Takemori, A. E. J. Med. Chem. 1986, 29, 1855-1861.
48. Choi, S. K. Synthetic Multivalent Molecules: Concepts and Biochemical Applications; Wiley-Interscience: Hoboken, NJ, 2004.
49. For reviews, see: (a) Mammen, M.; Choi, S.-K.; Whitesides, G. M. Angew. Chem., Int. Ed. 1998, 37, 2755-2794.
50. (b) Kiessling, L. L.; Gestwicki, J. E.; Strong, L. E. Curr. Opin. Chem. Biol. 2000, 4, 696-703.
51. (c) Kiessling, L. L.; Pohl, N. L. Chem. Biol. 1996, 3, 71-77.
52. For review, see: Kiessling, L. L.; Gestwicki, J. E.; Strong, L. E.; Angew. Chem., Int. Ed. 2006, 45, 2348-2368.
53. Selected examples: (a) Gestwicki, J. E.; Strong, L. E.; Kiessling, L. L. Chem. Biol. 2000, 7, 583-591.
54. (b) Gestwicki, J. E.; Kiessling, L. L. Nature 2002, 415, 81-84.
55. (c) Kramer, R. H.; Karpen, J. W. Nature 1998, 395, 710-713.
56. (d) Pattarawarapan, M.; Reyes, S.; Xia, Z.; Zaccaro, M. C.; Saragovi, H. U.; Burgess, K. J. Med. Chem. 2003, 46, 3565-3567.
57. (e) Puffer, E. B.; Pontrello, J. K.; Hollenbeck, J. J.; Kink, J. A.; Kiessling, L. L. ACS Chem. Biol. 2007, 2, 252-262.
58. Reviews on small molecule cytokine mimetics: (a) Whitty, A.; Borysenko, C. W. Chem. Biol. 1999, 6, R107-R118.
59. (a) Wrighton, N. C.; Farrell, F. X.; Chang, R.; Kashyap, A. K.; Barbone, F. P.; Mulcahy, L. S.; Johnson, D. L.; Barrett, R. W.; Jolliffe, L. K.; Dower, W. J. Science 1996, 273, 458-463.
60. (b) Livnah, O.; Stura, E. A.; Johnson, D. L.; Middleton, S. A.; Mulcahy, L. S.; Wrighton, N. C.; Dower, W. J.; Jolliffe, L. S. Wilson, I. A. Science 1996, 273, 464-471.
61. (c) Johnson, D. L.; Farrell, F. X.; Barbone, F. P.; McMahon, F. J.; Tullai, J.; Kroon, D.; Freedy, J.; Zivin, R. A.; Mulcahy, L. S.; Jolliffe, L. K. Chem. Biol. 1997, 4, 939-950.
62. (d) Cwirla, S. E.; Balasubramanian, P.; Duffin, D. J.; Wagstrom, C. R.; Gates, C. M.; Singer, S. C.; Davis, A. M.; Tansik, R. L.; Mattheakis, L. C.; Boytos, C. M.; Schatz, P. J.; Baccanari, D. P.; Wrighton, N. C.; Barrett, R. W.; Dower, W. J. Science 1997, 276, 1696-1699.
63. (e) Qureshi, S. A.; Kim, A. M.; Konteatis, Z.; Biazzo, D. E.; Motamedi, H.; Rodrigues, R.; Boice, J. A.; Calaycay, J. R.; Bednarek, M. A.; Griffin, P.; Gao, Y.-D.; Chapman, K.; Mark, D. F. Proc. Natl. Acad. Sci. U.S.A. 1999, 12, 12156-12161.
64. (f) Goldberg, J.; Jin, Q.; Ambroise, Y.; Satoh, S.; Desharnais, J.; Capps, K.; Boger, D. L. J. Am. Chem. Soc. 2002, 124, 544-555.
65. (g) Tian, S.-S.; Lamb, P.; King, A. G.; Miller, S. G.; Kessler, L.; Luengo, J. I.; Averill, L.; Johnson, R. K.; Gleason, J. G.; Pelus, L. M.; Dillon, S. B.; Rosen, J. Science 1998, 281, 257-259.
66. (h) Pattarawarapan, M.; Reyes, S.; Xia, Z.; Zaccaro, M. C.; Saragovi, H. U.; Burgess, K. J. Med. Chem. 2003, 46, 3565-3567.
67. (a) Bodmer, J. L.; Schneider, P.; Tschopp, J. Trends Biochem. Sci. 2002, 27, 19-26.
68. (b) Locksley, R. M.; Killen, N.; Lenardo, M. J. Cell 2001, 104, 487-501.
69. Although the conventional view is that members with the TNF-R family exist as independently diffusing monomeric species and trimerize upon ligand binding, some evidence suggests however, that several of these receptors may exist as pre-assembled oligomers prior to ligand binding. It has been shown that a conserved domain in the extracellular region of TNF-R, Trail receptor 1, and CD40, distal from the domain that interacts with the ligand, serves as a preligand-binding assembly domain (PLAD). Chan, F. K.; Chun, H. J.; Zheng, L.; Siegel, R. M.; Bui, K. L.; Lenardo, M. J. Science 2000, 288, 2351-2354.
70. For reviews, see: (a) van Kooten, C.; Banchereau, J. J. Leuk. Biol. 2000, 67, 1-17.
71. (b) Diehl, L.; Den, Boer, A. T.; van der Voort, E. I.; Melief, C. J.; Offringa, R.; Toes, R. E. J. Mol. Med. 2000, 78, 363-371.
72. (c) Grewal, I. S.; Flavell, R. A. Annu. Rev. Immunol. 1998, 16, 111-135.
73. (d) Van Kooten, C.; Banchereau, J. Adv. Immunol. 1996, 61, 1-77.
74. (e) Grewal, I. S.; Flavell, R.A. Immunol. Today 1996, 17, 410-414.
75. (f) Noelle, R. J. Immunity 1996, 4, 415-419.
76. (a) Howard, L. M.; Miga, A. J.; Vanderlugt, C. L.; Dal Canto, M. C.; Laman, J. D.; Noelle, R. J.; Miller, S. D. J. Clin. Invest. 1999, 103, 281-290.
77. (b) Kirk, A. D.; et al. Nat. Med. 1999, 5, 686-693.
78. Phase I/II studies in humans with lupus nephritis or multiple sclerosis revealed significant immunomodulatory effects of anti-CD40L monoclonal antibody treatment. However, because of some thromboembolic complications in early clinical trials, further human studies with anti-CD40L antibody have been temporary halted, and future clinical use is uncertain. See comment in: Couzin, J. Science 2005, 307, 1712-1715.
79. (a) Diehl, L.; den Boer, A. T.; Schoenberger, S. P.; van der Voort, E. I.; Schumacher, T. N.; Melief, C. J.; Offringa, R.; Toes, R. E. Nat. Med. 1999, 5, 774-779.
80. (b) van Mierlo, G. J.; den Boer, A. T.; Medema, J. P.; van der Voort, E. I.; Fransen, M. F.; Offringa, R.; Melief, C. J.; Toes, R. E. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5561-5566.
81. Karpusas, M.; Lucci, J.; Ferrant, J.; Benjamin, C.; Taylor, F. R.; Strauch, K.; Garber, E.; Hsu, Y. M. Structure 2001, 9, 421-429.
82. Singh, J.; Garber, E.; Van Vlijmen, H.; Karpusas, M.; Hsu, Y. M.; Zheng, Z.; Naismith, J.; Thomas, D. Protein Sci. 1998, 7, 1124-1135.
83. (a) Fournel, S.; Wieckowski, S.; Sun, W.; Trouche, N.; Dumortier, H.; Bianco, A.; Chaloin, O.; Habib, M.; Peter, J.-C.; Schneider, P.; Vray, B.; Toes, R. E.; Offringa, R.; Melief, C. J. M.; Hoebeke, J.; Guichard, G. Nat. Chem. Biol. 2005, 1, 377-382.
84. (b) Bianco, A.; Fournel, S.; Wieckowski, S.; Hoebeke, J.; Guichard, G. Org. Biomol. Chem. 2006, 4, 1461-1463.
85. (a) Hymowitz, S. G.; Ashkenazi, A. Nat. Chem. Biol. 2005, 1, 353-354.
86. (b) Gibson, S. E.; Castaldi, M. P. Angew. Chem., Int. Ed. 2006, 45, 4718-4720.
87. Habib, M.; Chamekh, M.; Noval, Rivas, M.; Wieckowski, S;, Sun, W.; Bianco, A.; Trouche, N.; Chaloin, O.; Dumortier, H.; Goldman, M.; Guichard, G.; Fournel, S.; Vray, B. J. Immunol. 2007, 178, 6700-6704.
88. Castro, B.; Dormoy, J. R.; Evin, G.; Selve, C. Tetrahedron Lett. 1975, 1219-1222.
89. Schuurhuis, D. H.; Laban, S.; Toes, R. E. M.; Ricciardi-Castagnoli, P.; Kleijmeer, M. J.; van der Voort, E. I. H.; Rea, D.; Offringa, O.; Geuze, H. J.; Melief, C. J. M.; Ossendorp, F. J. Exp. Med. 2000, 192, 145-150.
90. B lymphoma cells undergo apoptosis upon engagement of CD40 by recombinant CD40L. See: Frisan, T.; Donati, D.; Cervenak, L.; Wilson, J.; Masucci, M. G.; Bejarano, M. T. Int. J. Cancer 1999, 83, 772-779.
91. Bong, D. T.; Clark, T. D.; Granja, J. R.; Ghadiri, M. R. Angew. Chem., Int. Ed. 2001, 40, 988-1011 and refs therein.
92. Gac, S.; Zeng, X.; Reinaud, O.; Jabin, I. J. Org. Chem. 2005, 70, 1204-1210.
93. For use of calixarenes as multivalent templates and for the recognition of protein surfaces, see: (a) Baldini, L.; Casnati, A.; Sansone, F.; Ungaro, R. Chem. Soc. Rev. 2007, 36, 254-266.
94. (b) Reference 9g.
95. (c) Park, H. S.; Lin Q.; Hamilton, A. D. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5105-5109.
96. (d) Blaskovich, M. A.; Lin, Q.; Delarue, F. L.; Sun, J.; Park, H. S.; Coppola, D.; Hamilton, A. D.; Sebti, S. M. Nat. Biotechnol. 2000, 18, 1065-1070.
97. (e) Park, H. S.; Lin, Q.; Hamilton, A. D. J. Am. Chem. Soc. 1999; 121, 8-13.
98. 2) values which indicate that the accuracy of the fits are 0.43 and 0.85, respectively], suggesting that this interaction is of one miniCD40L for three CD40 receptors stoichiometry. Wieckowski, S.; Trouche, N.; Chaloin, O.; Guichard, G.; Fournel, S.; Hoebeke, J. Biochemistry, 2007, 46, 3482-3493.
99. D values for TNF family ligands binding to their cognate receptors and introduction of a "solution-phase Biacore binding assay", see : Day, E. S.; Cachero, T. G.; Qian, F.; Sun, Y.; Wen, D.; Pelletier, M.; Hsu, Y. M.; Whitty, A. Biochemistry 2005, 44, 1919-1931.
100. Quantification of A-1-mediated apoptosis in Burkitt lymphoma cells by an annexin V-propidium iodide colabeling technique (which enables the recognition of early and late apoptotic cells) and by terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL) gave comparable results (ref 26a and data not shown).
101. 3- symmetric cyclic D,L-hexapeptide structures, see: (a) Tomasi, L.; Lorenzi, G. P. Helv. Chim. Acta 1987, 70, 1012-1016.
102. (b) Saviano, M.; Lombardi, A.; Pedone, C.; Di, Blasio, B.; Sun, X. C.; Lorenzi, G. P. J. Incl. Phenom. 1994, 18, 27-36.
103. (c) Sun, X. C.; Lorenzi, G. P. Helv. Chim. Acta 1994, 77, 1520-1526.
104. 3 hexapeptides, see: Pavone, V.; Benedetti, E.; Di Blasio, B.; Lombardi, A.; Pedone, C.; Tomasich, L.; Lorenzi, G. Biopolymers 1989, 28, 215-223.
105. For studies on cyclic D,L-octapeptides, see: (a) Ghadiri, M. R.; Granja, J. R.; Milligan, R. A.; McRee, D. E.; Khazanovich, N. Nature 1993, 366, 324-327.
106. (b) Khazanovich, N.; Granja, J. R.; McRee, D. E.; Milligan, R. A.; Ghadiri, M. R. J. Am. Chem. Soc. 1994, 116, 6011-6012.
107. (c) Hartgerink, J. D.; Granja, J. R.; Milligan, R. A.; Ghadiri, M. R. J. Am. Chem. Soc. 1996, 118, 43-50.
108. 2O, see: Gademann, K.; Seebach, D. Helv. Chim. Acta 1999, 82, 957-962.
109. 4, see: Seebach, D.; Matthews, J. L.; Meden, A.; Wessels, T.; Baerlocher, C.; McCusker, L. B. Helv. Chim. Acta 1997, 80, 173-182.
110. Although cyclo-L,D-peptides show propensity to self-assemble into H-bonded tubular stacks in the solid state and in nonpolar solvents, there is no indication that A-1 aggregates in aqueous solution.
111. Kasai, N.; Yamanaka, T.; Miki, K.; Tanaka, N.; Post, B.; Morawetz, H. Acta Crystallogr., Sect. B 1981, 37, 1628-1630.
112. βC ranging from 2.62 to 2.75 Å. See: (a) Seebach, D.; Muller, H.-M.; Burger, H. M.; Plattner, D. A. Angew. Chem., Int. Ed. Engl. 1992, 31, 434.
113. (b) Seebach, D.; Hoffmann, T.; Kuhnle, F. N. M.; Lengweiler, U. D. Helv. Chim. Acta 1994, 77, 2007-2034.
114. Sridhar, J.; Wei, Z.-L.; Nowak, I.; Lewin, N. E.; Ayres, J. A.; Pearce, L. V.; Blumberg, P. M.; Kozikowski, A. P. J. Med. Chem. 2003, 46, 4196-4204.
115. Krishnamurthy, V. M.; Semetey, V.; Bracher, P. J.; Shen, N.; Whitesides, G. M. J. Am. Chem. Soc. 2007, 129, 1312-1320.
116. (a) Bajorath, J.; Chalupny, N. J.; Marken, J. S.; Siadak, A. W.; Skonier, J.; Gordon, M.; Hollenbaugh, D.; Noelle, R. J.; Ochs, H. D.; Aruffo, A. Biochemistry 1995, 34, 1833-1844.
117. (b) Bajorath, J.; Marken, J. S.; Chalupny, N. J.; Spoon, T. L.; Siadak, A. W.; Gordon, M.; Noelle, R. J.; Hollenbaugh, D.; Aruffo, A. Biochemistry 1995, 34, 9884-9892.
118. For reviews, see: (a) Venkatraman, J.; Shankaramma, S. C.; Balaram, P. Chem. Rev. 2001, 101, 3131-3152.
119. (b) Rose, G. D.; Gierasch, L. M.; Smith, J. A. Adv. Protein Chem. 1985, 37, 1-110.
120. D calculated using the Langmuir 1:1 model and local fitting models were 121 and 183 nM, respectively. Analysis of cooperativity using Hill plots suggested that the A-1/CD40 interaction is cooperative (Hill coefficient h = 2.9) and that this cooperativity is lost upon replacing Gly by D-Pro (h = 1.0).
121. Spatola, A. F. In Chemistry and Biochemistry of Amino Acids, Peptides and Proteins; Weinstein, B., Ed.; Marcel Dekker Inc.: New York, 1983; Vol. 7, pp 267-357.
122. Seebach, D; Schaeffer, L.; Brenner, M.; Hoyer, D. Angew. Chem., Int. Ed. 2003, 42, 776-778.
123. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953-956.
124. 2 = 0.843).
125. (a) Mierke, D. F.; Kurz, M.; Kessler, H. J. Am. Chem. Soc. 1994, 116, 1042-1049.
126. (b) Heller, M.; Sukopp, M.; Tsomaia, N.; John, M.; Mierke, D. F.; Reif, B.; Kessler, H. J. Am. Chem. Soc. 2006, 128, 13806-13814.
127. For selected examples of polyvalent systems based on cyclic peptide templates of different topology, see: (a) Singh, Y.; Dolphin, G. T.; Razkin, J.; Dumy, P. ChemBioChem 2006, 7, 1298-1314.
128. (b) Reference 10e.
129. (c) Zhang, Z.; Liu, J.; Verlinde, C. L. M. J.; Hol, W. G. J.; Fan, E. J. Org. Chem. 2004, 69, 7737-7740.
130. (a) Li, B.; Russell, S. J.; Compaan, D. M.; Totpal, K.; Marsters, S. A.; Ashkenazi, A.; Cochran, A. G.; Hymowitz, S. G.; Sidhu, S. S. J. Mol. Biol. 2006, 361, 522-36.
131. (b) Angell, Y. M.; et al. In Understanding Biology Using Peptides; Blondelle, S. E., Ed.; Proceedings of the Nineteenth American Peptide Symposium, Series: American Peptide Symposia, Vol. 9; Springer: New York, 2006; pp 405-406.
132. Harbury, P. B.; Zhang, T.; Kim, P. S.; Alber, T. Science, 1993, 262, 1401-1407.
133. McWhirter, S. M.; Pullen, S. S.; Holton, J. M.; Crute, J. J.; Kehry, M. R.; Alber, T. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 8408-8413.
134. Hakansson, K.; Reid, K. B. Protein Sci. 2000, 9, 1607-1617.
135. Kishore, U.; Gaboriaud, C.; Waters, P.; Shrive, A. K.; Greenhough, T. J.; Reid, K. B.; Sim, R. B.; Arlaud, G. J. Trends Immunol. 2004, 25, 551-561.
136. Bewley, M. C.; Springer, K.; Zhang, Y. B.; Freimuth, P.; Flanagan, J. M. Science 1999, 286, 1579-1583.
137. Zhu, P.; Liu, J.; Bess, J., Jr.; Chertova, E.; Lifson, J. D.; Grise, H.; Ofek, G. A.; Taylor, K. A.; Roux, K. H. Nature 2006, 441, 847-852.
138. 4-binding sites on the HIV-1 Env glycoprotein gp120 trimers have been reported recently. Li, H.; Guan, Y.; Szczepanska, A.; Moreno-Vargas, A. J.; Carmona, A. T.; Robina, I.; Lewis, G. K.; Wang, L. X. Bioorg. Med. Chem. 2007, 15, 4220-4228.
139. Holler, N.; Tardivel, A.; Kovacsovics-Bankowski, M.; Hertig, S.; Gaide, O.; Martinon, F.; Tinel, A.; Deperthes, D.; Calderara, S.; Schulthess, T.; Engel, J.; Schneider, P.; Tschopp, J. Mol. Cell. Biol. 2003, 23, 1428-1440.