Design, synthesis, and functionalization of dimeric peptides targeting chemokine receptor CXCR4

Journal of Medicinal Chemistry

Volumn 54, Issue 21, 2011, Pages 7648-7662

  Demmer, Oliver ^a   Dijkgraaf, Ingrid ^a   Schumacher, Udo ^b   Marinelli, Luciana ^c   Cosconati, Sandro ^c   Gourni, Eleni ^a   Wester, Hans Jürgen ^a   Kessler, Horst ^a,d  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^d KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

Author keywords

[No Author keywords available]

Indexed keywords

1,4,7,10 TETRAAZACYCLODODECANE 1,4,7,10 TETRAACETIC ACID; CHELATING AGENT; CHEMOKINE RECEPTOR CXCR4; GALLIUM 68; PENTAPEPTIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONJUGATION; CONTROLLED STUDY; DRUG DESIGN; DRUG SYNTHESIS; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNOSURVEILLANCE; ISOTOPE LABELING; METASTASIS; MOLECULAR IMAGING; MOUSE; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PROTEIN FUNCTION; PROTEIN TARGETING; TISSUE DISTRIBUTION;

ANIMALS; BINDING SITES; CHELATING AGENTS; COORDINATION COMPLEXES; DIMERIZATION; DRUG DESIGN; GADOLINIUM; HETEROCYCLIC COMPOUNDS, 1-RING; LIGANDS; MICE; MICE, NUDE; MODELS, MOLECULAR; OLIGOPEPTIDES; PEPTIDES, CYCLIC; POSITRON-EMISSION TOMOGRAPHY; PROTEIN BINDING; RADIOPHARMACEUTICALS; RECEPTORS, CXCR4; STRUCTURE-ACTIVITY RELATIONSHIP; TISSUE DISTRIBUTION;

EID: 80455162590     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2009716     Document Type: Article

References (108)

1. Nagasawa, T.; Kikutani, H.; Kishimoto, T. Molecular cloning and structure of a pre-B-cell growth-stimulating factor Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 2305-2309
2. Oberlin, E.; Amara, A.; Bachelerie, F.; Bessia, C.; Virelizier, J. L.; Arenzana-Seisdedos, F.; Schwartz, O.; Heard, J. M.; Clark-Lewis, I.; Legler, D. F.; Loetscher, M.; Baggiolini, M.; Moser, B. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1 Nature 1996, 382, 833-835
3. Tashiro, K.; Tada, H.; Heilker, R.; Shirozu, M.; Nakano, T.; Honjo, T. Signal Sequence Trap-A Cloning Strategy for Secreted Proteins and Type-I Membrane-Proteins Science 1993, 261, 600-603
4. Bleul, C. C.; Farzan, M.; Choe, H.; Parolin, C.; Clark-Lewis, I.; Sodroski, J.; Springer, T. A. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry Nature 1996, 382, 829-833
5. Busillo, J. M.; Benovic, J. L. Regulation of CXCR4 signaling Biochem. Biophys. Acta: Biomembranes 2007, 1768, 952-963
6. Burger, M.; Hartmann, T.; Krome, M.; Rawluk, J.; Tamamura, H.; Fujii, N.; Kipps, T. J.; Burger, J. A. Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells Blood 2005, 106, 1824-1830
7. Murdoch, C. CXCR4: chemokine receptor extraordinaire Immunol. Rev. 2000, 177, 175-184
8. Klein, R. S.; Rubin, J. B. Immune and nervous system CXCL12 and CXCR4: parallel roles in patterning and plasticity Trends Immunol. 2004, 25, 306-314
9. Tamamura, H.; Fujii, N. The therapeutic potential of CXCR4 antagonists in the treatment of HIV infection, cancer metastasis and rheumatoid arthritis Expert Opin. Ther. Targets 2005, 9, 1267-1282
10. De Clercq, E. New approaches toward anti-HIV chemotherapy J. Med. Chem. 2005, 48, 1297-1313
11. Tsutsumi, H.; Tamamura, H.; Fujii, N. Inhibitors of the chemokine receptor CXCR4: Chemotherapy of AIDS, metastatic cancer, leukemia and rheumatoid arthritis Lett. Drug Des. Discovery 2007, 4, 20-26
12. De Clercq, E. Potential clinical applications of the CXCR4 antagonist bicyclam AMD3100 Mini-Rev. Med. Chem. 2005, 5, 805-824
13. Burger, J. A.; Kipps, T. J. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment Blood 2006, 107, 1761-1767
14. Wong, D.; Korz, W. Translating an antagonist of chemokine receptor CXCR4: from bench to bedside Clin. Cancer Res. 2008, 14, 7975-7980
15. Khan, A.; Greenman, J.; Archibald, S. J. Small molecule CXCR4 chemokine receptor antagonists: developing drug candidates Curr. Med. Chem. 2007, 14, 2257-2277
16. Levesque, J. P.; Winkler, I. G. Mobilization of hematopoietic stem cells: state of the art Curr. Opin. Organ Transplant. 2008, 13, 53-58
17. White, F. A.; Wilson, N. M. Chemokines as pain mediators and modulators Curr. Opin. Anaesthesiol. 2008, 21, 580-585
18. Bhangoo, S. K.; Ren, D.; Miller, R. J.; Chan, D. M.; Ripsch, M. S.; Weiss, C.; McGinnis, C.; White, F. A. CXCR4 chemokine receptor signaling mediates pain hypersensitivity in association with antiretroviral toxic neuropathy Brain Behav. Immunol. 2007, 21, 581-591
19. Savarin-Vuaillat, C.; Ransohoff, R. M. Chemokines and chemokine receptors in neurological disease: raise, retain, or reduce? Neurotherapeutics 2007, 4, 590-601
20. Mines, M.; Ding, Y.; Fan, G. H. The many roles of chemokine receptors in neurodegenerative disorders: emerging new therapeutical strategies Curr. Med. Chem. 2007, 14, 2456-2470
21. Mélik-Parsadaniantz, S.; Rostène, W. Chemokines and neuromodulation J. Neuroimmunol. 2008, 198, 62-68
22. Aime, S.; Castelli, D. D.; Crich, S. G.; Gianolio, E.; Terreno, E. Pushing the Sensitivity Envelope of Lanthanide-Based Magnetic Resonance Imaging (MRI) Contrast Agents for Molecular Imaging Applications Acc. Chem. Res. 2009, 42, 822-831
23. Shokeen, M.; Anderson, C. J. Molecular Imaging of Cancer with Copper-64 Radiopharmaceuticals and Positron Emission Tomography (PET) Acc. Chem. Res. 2009, 42, 832-841
24. De Jong, M.; Breeman, W. A. P.; Kwekkeboom, D. J.; Valkema, R.; Krenning, E. P. Tumor Imaging and Therapy Using Radiolabeled Somatostatin Analogues Acc. Chem. Res. 2009, 42, 873-880
25. Major, J. L.; Meade, T. J. Bioresponsive, Cell-Penetrating, and Multimeric MR Contrast Agents Acc. Chem. Res. 2009, 42, 893-903
26. Tweedle, M. F. Peptide-Targeted Diagnostics and Radiotherapeutics Acc. Chem. Res. 2009, 42, 958-968
27. Schottelius, M.; Laufer, B.; Kessler, H.; Wester, H. J. Ligands for Mapping alpha(v)beta(3)-Integrin Expression in Vivo Acc. Chem. Res. 2009, 42, 969-980
28. Thumshirn, G.; Hersel, U.; Goodman, S. L.; Kessler, H. Multimeric cyclic RGD peptides as potential tools for tumor targeting: Solid-phase peptide synthesis and chemoselective oxime ligation Chem.-Eur. J. 2003, 9, 2717-2725
29. Poethko, T.; Schottelius, M.; Thumshirn, G.; Herz, M.; Haubner, R.; Henriksen, G.; Kessler, H.; Schwaiger, M.; Wester, H. J. Chemoselective pre-conjugate radiohalogenation of unprotected mono- and multimeric peptides via oxime formation Radiochim. Acta 2004, 92, 317-327
30. Vagner, J.; Handl, H. L.; Monguchi, Y.; Jana, U.; Begay, L. J.; Mash, E. A.; Hruby, V. J.; Gillies, R. J. Rigid linkers for bioactive peptides Bioconjugate Chem. 2006, 17, 1545-1550
31. Wester, H. J.; Kessler, H. Molecular targeting with peptides or peptide-polymer conjugates: Just a question of size? J. Nucl. Med. 2005, 46, 1940-1945
32. Kessler, H.; Schudok, M.; Haupt, A. In Peptides; Jung, G.; Bayer, E., Eds.; Walter de Gruyter: Tübingen, Germany, 1988; pp 664-666.
33. Mammen, M.; Choi, S. K.; Whitesides, G. M. Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors Angew. Chem. Int. Ed. 1998, 37, 2755-2794
34. Kiessling, L. L.; Gestwicki, J. E.; Strong, L. E. Synthetic multivalent ligands as probes of signal transduction Angew. Chem., Int. Ed. Engl. 2006, 45, 2348-2368
35. 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, 6996-7007
36. De Clercq, E.; Yamamoto, N.; Pauwels, R.; Balzarini, J.; Witvrouw, M.; De Vreese, K.; Debyser, Z.; Rosenwirth, B.; Peichl, P.; Datema, R. Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100 Antimicrob. Agents Chemother. 1994, 38, 668-674
37. De Clercq, E. The AMD3100 story: the path to the discovery of a stem cell mobilizer (Mozobil) Biochem. Pharmacol. 2009, 77, 1655-1664
38. Zhan, W. Q.; Liang, Z. X.; Zhu, A. Z.; Kurtkaya, S.; Shim, H.; Snyder, J. P.; Liotta, D. C. Discovery of small molecule CXCR4 antagonists J. Med. Chem. 2007, 50, 5655-5664
39. Ojida, A.; Mito-oka, Y.; Inoue, M.; Hamachi, I. First artificial receptors and chemosensors toward phosphorylated peptide in aqueous solution J. Am. Chem. Soc. 2002, 124, 6256-6258
40. Loetscher, P.; Gong, J. H.; Dewald, B.; Baggiolini, M.; Clark-Lewis, I. N-Terminal peptides of stromal cell-derived factor-1 with CXC chemokine receptor 4 agonist and antagonist activities J. Biol. Chem. 1998, 273, 22279-22283
41. Liang, X. CXCR4, inhibitors and mechanisms of action Chem. Biol. Drug Des. 2008, 72, 97-110
42. Heveker, N.; Tissot, M.; Thuret, A.; Schneider-Mergener, J.; Alizon, M.; Roch, M.; Marullo, S. Pharmacological properties of peptides derived from stromal cell-derived factor 1: study on human polymorphonuclear cells Mol. Pharmacol. 2001, 59, 1418-1425
43. Tamamura, H.; Ojida, A.; Ogawa, T.; Tsutsumi, H.; Masuno, H.; Nakashima, H.; Yamamoto, N.; Hamachi, I.; Fujii, N. Identification of a new class of low molecular weight antagonists against the chemokine receptor CXCR4 having the dipicolylamine-zinc(II) complex structure J. Med. Chem. 2006, 49, 3412-3415
44. Faber, A.; Roderburg, C.; Wein, F.; Saffrich, R.; Seckinger, A.; Horsch, K.; Diehlmann, A.; Wong, D.; Bridger, G.; Eckstein, V.; Ho, A. D.; Wagner, W. The many facets of SDF-1 alpha, CXCR4 agonists and antagonists on hematopoietic progenitor cells J. Biomed. Biotechnol. 2007, 10
45. Hereld, D.; Jin, T. Slamming the DOR on chemokine receptor signaling: Heterodimerization silences ligand-occupied CXCR4 and delta-opioid receptors Eur. J. Immunol. 2008, 38, 334-337
46. Levoye, A.; Balabanian, K.; Baleux, F.; Bachelerie, F.; Lagane, B. CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling Blood 2009, 113, 6085-6093
47. 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, 1066-1071
48. Kiessling, L. L.; Gestwicki, J. E.; Strong, L. E. Synthetic multivalent ligands in the exploration of cell-surface interactions Curr. Opin. Chem. Biol. 2000, 4, 696-703
49. Gazit, A.; Osherov, N.; Gilon, C.; Levitzki, A. Tyrphostins. 6. Dimeric benzylidenemalononitrile tyrophostins: potent inhibitors of EGF receptor tyrosine kinase in vitro J. Med. Chem. 1996, 39, 4905-4911
50. Poethko, T.; Schottelius, M.; Thumshirn, G.; Hersel, U.; Herz, M.; Henriksen, G.; Kessler, H.; Schwaiger, M.; Wester, H. J. Two-step methodology for high-yield routine radiohalogenation of peptides: F-18-labeled RGD and octreotide analogs J. Nucl. Med. 2004, 45, 892-902
51. 68Ga-labeled multimeric RGD peptides for microPET imaging of integrin alpha(v)beta(3) expression Eur. J. Nucl. Med. Mol. Imaging 2008, 35, 1100-1108
52. Miyata, T.; Tokunaga, F.; Yoneya, T.; Yoshikawa, K.; Iwanaga, S.; Niwa, M.; Takao, T.; Shimonishi, Y. Antimicrobial peptides, isolated from horseshoe crab hemocytes, tachyplesin II, and polyphemusins I and II: chemical structures and biological activity J. Biochem. (Tokyo) 1989, 106, 663-668
53. Tamamura, H.; Xu, Y. O.; Hattori, T.; Zhang, X. Y.; Arakaki, R.; Kanbara, K.; Omagari, A.; Otaka, A.; Ibuka, T.; Yamamoto, N.; Nakashima, H.; Fujii, N. A low-molecular-weight inhibitor against the chemokine receptor CXCR4: A strong anti-HIV peptide T140 Biochem. Biophys. Res. Commun. 1998, 253, 877-882
54. 7]-Polyphemusin-II) Biochem. Biophys. Res. Commun. 1992, 189, 845-850
55. Tamamura, H.; Waki, M.; Imai, M.; Otaka, A.; Ibuka, T.; Waki, K.; Miyamoto, K.; Matsumoto, A.; Murakami, T.; Nakashima, H.; Yamamoto, N.; Fujii, N. Downsizing of an HIV-cell fusion inhibitor, T22 ([Tyr(5,12), Lys(7)]-polyphemusin II), with the maintenance of anti-HIV activity and solution structure Bioorg. Med. Chem. 1998, 6, 473-479
56. 7]-polyphemusin II) Bioorg. Med. Chem. 1998, 6, 231-238
57. Tamamura, H.; Omagari, A.; Oishi, S.; Kanamoto, T.; Yamamoto, N.; Peiper, S. C.; Nakashima, H.; Otaka, A.; Fujii, N. Pharmacophore identification of a specific CXCR4 inhibitor, T140, leads to development of effective anti-HIV agents with very high selectivity indexes Bioorg. Med. Chem. Lett. 2000, 10, 2633-2637
58. Fujii, N.; Oishi, S.; Hiramatsu, K.; Araki, T.; Ueda, S.; Tamamura, H.; Otaka, A.; Kusano, S.; Terakubo, S.; Nakashima, H.; Broach, J. A.; Trent, J. O.; Wang, Z. X.; Peiper, S. C. Molecular-size reduction of a potent CXCR4-chemokine antagonist using orthogonal combination of conformation- and sequence-based libraries Angew. Chem. Int. Ed. 2003, 42, 3251-3253
59. Haubner, R.; Kuhnast, B.; Mang, C.; Weber, W. A.; Kessler, H.; Wester, H. J.; Schwaiger, M. [F-18]Galacto-RGD: Synthesis, radiolabeling, metabolic stability, and radiation dose estimates Bioconjugate Chem. 2004, 15, 61-69
60. Zhang, W. B.; Navenot, J. M.; Haribabu, B.; Tamamura, H.; Hiramatu, K.; Omagari, A.; Pei, G.; Manfredi, J. P.; Fujii, N.; Broach, J. R.; Peiper, S. C. A point mutation that confers constitutive activity to CXCR4 reveals that T140 is an inverse agonist and that AMD3100 and ALX40-4C axe weak partial agonists J. Biol. Chem. 2002, 277, 24515-24521
61. Trent, J. O.; Wang, Z. X.; Murray, J. L.; Shao, W.; Tamamura, H.; Fujii, N.; Peiper, S. C. Lipid bilayer simulations of CXCR4 with inverse agonists and weak partial agonists J. Biol. Chem. 2003, 278, 47136-47144
62. Wang, Z.-x.; Tamamura, H.; Frilot, N.; Broach, J.; Fujii, N.; Peiper, S. Screening and characterization of cyclic pentapeptide CXCR4 antagonists/inverse agonists using a pheromone responsive reporter gene in Saccharomyces cerevisiae: Utility of G protein coupled receptor constitutively active mutants. In Chemokine Biology-Basic Research and Clinical Application; Neote; K. L.; Gordon, L.; Moser, B., Eds.; Birkhäuser: Basel, 2007; pp 61-77.
63. 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, 15899-901
64. Ueda, S.; Oishi, S.; Wang, Z. X.; Araki, T.; Tamamura, H.; Cluzeau, J.; Ohno, H.; Kusano, S.; Nakashima, H.; Trent, J. O.; Peiper, S. C.; Fujii, N. Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities J. Med. Chem. 2007, 50, 192-198
65. Demmer, O.; Koglin, N.; Kessler, H.; Wester, H. J. Cyclic peptides for targeting CXCR4 chemokine receptor expression J. Pept. Sci. 2006, 12, 172-172
66. Demmer, O.; Gourni, E.; Schumacher, U.; Wester, H. J.; Kessler, H. PET imaging of CXCR4 receptors in cancer by a new optimized ligand. ChemMedChem, 2011, DOI 10.1002/cmdc.201100320
67. Demmer, O.; Dijkgraaf, I.; Schottelius, M.; Wester, H. J.; Kessler, H. Introduction of functional groups into peptides via N -alkylation Org. Lett. 2008, 10, 2015-2018
68. Demmer, O.; Frank, A. O.; Kessler, H. Design of Cyclic Peptides. In Design of Peptides and Proteins for Biopharmaceutical Applications: Applications for Therapeutic Agents and Biomedical Research; Jensen, K. J., Ed.; Wiley: New York, 2009; pp 133-176.
69. Kessler, H.; Kutscher, B. Peptide Conformations 0.40. Cyclic Hexapeptide Analogs of Thymopoietin-Synthesis and Conformational Analysis Liebigs Ann. Chem. 1986, 914-931
70. Gilon, C.; Mang, C.; Lohof, E.; Friedler, A.; Kessler, H. Synthesis of Peptides and Peptidomimetics. In Houben-Weyl: Methods of Organic Chemistry; Goodman, M.; Felix, L.; Moroder, L.; Toniolo, C., Eds.; Thieme Verlag: Stuttgart, 2003; pp 461-542.
71. Biron, E.; Chatterjee, J.; Kessler, H. Optimized selective N -methylation of peptides on solid support J. Pept. Sci. 2006, 12, 213-219
72. Müller, A.; Vogt, C.; Sewald, N. Synthesis of Fmoc-beta-homoamino acids by ultrasound-promoted Wolff rearrangement Synthesis (Stuttgart) 1998, 837-841
73. Moepps, B.; Frodl, R.; Rodewald, H. R.; Baggiolini, M.; Gierschik, P. Two murine homologues of the human chemokine receptor CXCR4 mediating stromal cell-derived factor 1 alpha activation of G(12) are differentially expressed in vivo Eur. J. Immunol. 1997, 27, 2102-2112
74. Hanaoka, H.; Mukai, T.; Tamamura, H.; Mori, T.; Ishino, S.; Ogawa, K.; Iida, Y.; Doi, R.; Fujii, N.; Saji, H. Development of a In-111-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors Nucl. Med. Biol. 2006, 33, 489-494
75. Jacobson, O.; Weiss, I. D.; Szajek, L.; Farber, J. M.; Kiesewetter, D. O. Cu-64-AMD3100-a novel imaging agent for targeting chemokine receptor CXCR4 Bioorg. Med. Chem. 2009, 17, 1486-1493
76. Nimmagadda, S.; Pullambhatla, M.; Stone, K.; Green, G.; Bhujwalla, Z. M.; Pomper, M. G. Molecular Imaging of CXCR4 Receptor Expression in Human Cancer Xenografts with [Cu-64]AMD3100 Positron Emission Tomography Cancer Res. 2010, 70, 3935-3944
77. Ichiyama, K.; Yokoyama-Kumakura, S.; Tanaka, Y.; Tanaka, R.; Hirose, K.; Bannai, K.; Edamatsu, T.; Yanaka, M.; Niitani, Y.; Miyano-Kurosaki, N.; Takaku, H.; Koyanagi, Y.; Yamamoto, N. A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 4185-4190
78. Fujii, N.; Nakashima, H.; Tamamura, H. The therapeutic potential of CXCR4 antagonists in the treatment of HIV Expert Opin. Invest. Drug 2003, 12, 185-195
79. Friesner, R. A.; Murphy, R. B.; Repasky, M. P.; Frye, L. L.; Greenwood, J. R.; Halgren, T. A.; Sanschagrin, P. C.; Mainz, D. T. Extra precision Glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes J. Med. Chem. 2006, 49, 6177-6196
80. Clark-Lewis, I.; Kim, K. S.; Rajarathnam, K.; Gong, J. H.; Dewald, B.; Moser, B.; Baggiolini, M.; Sykes, B. D. Structure-activity relationships of chemokines J. Leukocyte Biol. 1995, 57, 703-11
81. Wells, T. N.; Power, C. A.; Lusti-Narasimhan, M.; Hoogewerf, A. J.; Cooke, R. M.; Chung, C. W.; Peitsch, M. C.; Proudfoot, A. E. Selectivity and antagonism of chemokine receptors J. Leukocyte Biol. 1996, 59, 53-60
82. Gupta, S. K.; Pillarisetti, K.; Thomas, R. A.; Aiyar, N. Pharmacological evidence for complex and multiple site interaction of CXCR4 with SDF-1alpha: implications for development of selective CXCR4 antagonists Immunol. Lett. 2001, 78, 29-34
83. 262 in the CXCR4 receptor Biochemistry 2003, 42, 710-717
84. Khan, A.; Silversides, J. D.; Madden, L.; Greenman, J.; Archibald, S. J. Fluorescent CXCR4 chemokine receptor antagonists: metal activated binding Chem. Commun. (Cambridge, UK) 2007, 416-418
85. Khan, A.; Nicholson, G.; Greenman, J.; Madden, L.; McRobbie, G.; Pannecouque, C.; De Clercq, E.; Ullom, R.; Maples, D. L.; Maples, R. D.; Silversides, J. D.; Hubin, T. J.; Archibald, S. J. Binding Optimization through Coordination Chemistry: CXCR4 Chemokine Receptor Antagonists from Ultrarigid Metal Complexes J. Am. Chem. Soc. 2009, 131, 3416-3417
86. Heppeler, A.; Froidevaux, S.; Mäcke, H. R.; Jermann, E.; Béhé, M.; Powell, P.; Hennig, M. Radiometal-Labelled Macrocyclic Chelator-Derivatised Somatostatin Analogue with Superb Tumour-Targeting Properties and Potential for Receptor-Mediated Internal Radiotherapy Chem. Eur. J. 1999, 5, 1974-1981
87. 111In-Labeled DOTA-Biomolecule Conjugates Inorg. Chem. 2003, 42, 8831-8837
88. Reubi, J. C.; Schar, J. C.; Waser, B.; Wenger, S.; Heppeler, A.; Schmitt, J. S.; Mäcke, H. R. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use Eur. J. Nucl. Med. 2000, 27, 273-282
89. 3-amino acids from Fmoc-(R)-beta-HAsp(OtBu)-OH Tetrahedron Lett. 2003, 44, 6079-6082
90. Herzner, H.; Kunz, H. Spacer-separated sialyl LewisX cyclopeptide conjugates as potential E-selectin ligands Carbohydr. Res. 2007, 342, 541-557
91. Castonguay, R.; Lherbet, C.; Keillor, J. W. Mapping of the active site of rat kidney gamma-glutamyl transpeptidase using activated esters and their amide derivatives Bioorg. Med. Chem. 2002, 10, 4185-4191
92. Mizukami, S.; Takikawa, R.; Sugihara, F.; Hori, Y.; Tochio, H.; Walchli, M.; Shirakawa, M.; Kikuchi, K. Paramagnetic relaxation-based F-19 MRI probe to detect protease activity J. Am. Chem. Soc. 2008, 130, 794-795
93. Wishart, D. S.; Bigam, C. G.; Yao, J.; Abildgaard, F.; Dyson, H. J.; Oldfield, E.; Markley, J. L.; Sykes, B. D. 1H, 13C and 15N chemical shift referencing in biomolecular NMR J. Biomol. NMR 1995, 6, 135-140
94. Piotto, M.; Saudek, V.; Sklenar, V. Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions J. Biomol. NMR 1992, 2, 661-665
95. Kessler, H.; Seip, S. NMR of Peptides. In Two-Dimensional NMR-Spectroscopy, Applications for Chemists and Biochemists; Croasmun, W. R.; Carlson, M. K., Eds.; VCH: New York, 1994; pp 619-654.
96. Kessler, H.; Schmitt, W. Peptides and Polypeptides. In Encyclopedia of Nuclear Magnetic Resonance; Grant, D. M.; Harris, R. K., Eds.; J. Wiley & Sons: New York, 1996; pp 3527-3537.
97. Bax, A.; Summers, M. F. H-1 and C-13 Assignments from Sensitivity-Enhanced Detection of Heteronuclear Multiple-Bond Connectivity by 2d Multiple Quantum Nmr J. Am. Chem. Soc. 1986, 108, 2093-2094
98. Bermel, W.; Wagner, K.; Griesinger, C. Proton-Detected C,H Correlation Via Long-Range Couplings with Soft Pulses-Determination of Coupling-Constants J. Magn. Reson. 1989, 83, 223-232
99. Kessler, H.; Schmieder, P.; Kock, M.; Kurz, M. Improved Resolution in Proton-Detected Heteronuclear Long-Range Correlation J. Magn. Reson. 1990, 88, 615-618
100. Griesinger, C.; Sorensen, O. W.; Ernst, R. R. Practical Aspects of the E-Cosy Technique-Measurement of Scalar Spin Spin Coupling Constants in Peptides J. Magn. Reson. 1987, 75, 474-492
101. Bothner-By, A. A.; Stephens, R. L.; Lee, J. M.; Warren, C. D.; Jeanloz, R. W. Structure Determination of a Tetrasaccharide-Transient Nuclear Overhauser Effects in the Rotating Frame J. Am. Chem. Soc. 1984, 106, 811-813
102. Kessler, H.; Griesinger, C.; Kerssebaum, R.; Wagner, K.; Ernst, R. R. Separation of Cross-Relaxation and J-Cross-Peaks in 2D Rotating-Frame NMR Spectroscopy J. Am. Chem. Soc. 1987, 109, 607-609
103. Berendsen, H. J. C.; van der Spoel, D.; van Drunen, R. GROMACS: A message-passing parallel molecular dynamics implementation Comput. Phys. Commun. 1995, 91, 43-56
104. Lindahl, E.; Hess, B.; van der Spoel, D. GROMACS 3.0: A package for molecular simulation and trajectory analysis J. Mol. Model. 2001, 7, 306-317
105. Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.; Dinola, A.; Haak, J. R. Molecular Dynamics with Coupling to an External Bath J. Chem. Phys. 1984, 81, 3684-3690
106. Schrödinger Suite 2009 Protein Preparation Wizard, Epik version 2.0; Impact version 5.5; Prime version 2.1; Schrödinger, LLC: New York, NY, 2009.
107. Friesner, R. A.; Murphy, R. B.; Repasky, M. P.; Frye, L. L.; Greenwood, J. R.; Halgren, T. A.; Sanschagrin, P. C.; Mainz, D. T. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes J. Med. Chem. 2006, 49, 6177-6196
108. 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, 1605-12