A journey in structure-based drug discovery: From designed peptides to protein surface topomimetics as antibiotic and antiangiogenic agents

Accounts of Chemical Research

Volumn 40, Issue 10, 2007, Pages 1057-1065

  Dings, Ruud P M ^a   Mayo, Kevin H ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTIINFECTIVE AGENT; PEPTIDE; PROTEIN;

AMINO ACID SEQUENCE; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; MOLECULAR GENETICS; MOLECULAR MIMICRY; STRUCTURE ACTIVITY RELATION; SURFACE PROPERTY;

AMINO ACID SEQUENCE; ANGIOGENESIS INHIBITORS; ANTI-BACTERIAL AGENTS; DRUG DESIGN; MODELS, MOLECULAR; MOLECULAR MIMICRY; MOLECULAR SEQUENCE DATA; PEPTIDES; PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; SURFACE PROPERTIES;

EID: 35948946972     PISSN: 00014842     EISSN: None     Source Type: Journal    
DOI: 10.1021/ar700086k     Document Type: Article

References (74)

1. Nagar, B.; Hantschel, O.; Young, M. A.; Scheffzek, K.; Veach, D.; Bornmann, W.; Clarkson, B.; Superti-Furga, G.; Kuriyan, J. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell 2003, 112, 859-871.
2. Drews, J. Drug discovery: a historical perspective. Science 2000, 287, 1960-1964.
3. Orsini, M. J.; Nesmelova, I.; Young, H. C.; Hargittai, B.; Beavers, M. P.; Liu, J.; Connolly, P. J.; Middleton, S. A.; Mayo, K. H. The nociceptin pharmacophore site for opioid receptor binding derived from the NMR structure and bioactivity relationships. J. Biol. Chem. 2005, 280, 8134-8142.
4. Orsini, M. J.; Klein, M. A.; Beavers, M. P.; Connolly, P. J.; Middleton, S. A.; Mayo, K. H. Metastin (KiSS-1) mimetics identified from peptide structure-activity relationship-derived pharmacophores and directed small molecule database screening. J. Med. Chem. 2007, 50, 462-471.
5. Ilyina, E.; Mayo, K. H. Multiple native-like conformations trapped via self-association-induced hydrophobic collapse of the 33-residue beta-sheet domain from platelet factor 4. Biochem. J. 1995, 306, 407-419.
6. Mayo, K. H.; Ilyina, E.; Park, H. A recipe for designing water-soluble, beta-sheet-forming peptides. Protein Sci. 1996, 5, 1301-1315.
7. Ilyina, E.; Roongta, V.; Mayo, K. H. NMR structure of a de novo designed, peptide 33mer with two distinct, compact beta-sheet folds. Biochemistry 1997, 36, 5245-5250.
8. Cox, A.; Arroyo, M. M.; Mayo, K. H. Folding of beta pep-4 beta-sheet sandwich dimers and tetramers is influenced by aliphatic hydrophobic residues at the intersubunit interface. Biochem. J. 2001, 357, 739-747.
9. Gray, B. H.; Haseman, J. R.; Mayo, K. H. B/PI-derived synthetic peptides: synergistic effects in tethered bactericidal and endotoxin neutralizing peptides. Biochem. Biophys. Acta 1995, 1244, 185-190.
10. Hoess, A.; Watson, S.; Siber, G. R.; Liddington, R. Crystal structure of an endotoxin-neutralizing protein from the horseshoe crab, Limulus anti-LPS factor, at 1.5 A resolution. EMBO J. 1993, 12, 3351-3356.
11. Beamer, L. J.; Carroll, S. F.; Eisenberg, D. Crystal structure of human BPI and two bound phospholipids at 2.4 angstrom resolution. Science 1997, 276, 1861-1864.
12. Mayo, K. H.; Haseman, J.; Ilyina, E.; Gray, B. Designed beta-sheet-forming peptide 33mers with potent human bactericidal/permeability increasing protein-like bactericidal and endotoxin neutralizing activities. Biochim. Biophys. Acta 1998, 1425, 81-92.
13. Mayo, K. H.; Haseman, J. R.; Ilyina, E.; Gray, B. Designed beta-sheet-forming peptide 33mers with potent human bactericidal/permeability increasing protein-like bactericidal and endotoxin neutralizing activities. Biochem. Biophys. Acta 1998, 1425, 81-92.
14. Lockwood, N. A.; Mayo, K. H. The future of antibiotics: bacterial membrane disintegrators. Drugs Future 2003, 28, 911-923.
15. Mayo, K. H.; Haseman, J.; Young, H. C.; Mayo, J. W. Structure-function relationships in novel peptide dodecamerswith broadspectrum bactericidal and endotoxin-neutralizing activities. Biochem. J. 2000, 349, 717-728.
16. D'Andrea, L. D.; Del Gatto, A.; Pedone, C.; Benedetti, E. Peptide-based molecules in angiogenesis. Chem. Biol. Drug Des. 2006, 67, 115-126.
17. Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 1971, 285, 1182-1186.
18. Folkman, J. The role of angiogenesis in tumor growth. Semin. Cancer Biol. 1992, 3, 65-71.
19. Boehm, T.; Folkman, J.; Browder, T.; O'Reilly, M. S. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature (London) 1997, 390, 404-407.
20. O'Reilly, M. S.; Holmgren, L.; Shing, Y.; Chen, C.; Rosenthal, R. A.; Moses, M.; Lane, W. S.; Cao, Y.; Sage, E. H.; Folkman, J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994, 79, 315-328.
21. O'Reilly, M. S.; Boehm, T.; Shing, Y.; Fukai, N.; Vasios, G.; Lane, W. S.; Flynn, E.; Birkhead, J. R.; Olsen, B. R.; Folkman, J. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997, 88, 277-285.
22. Griffin, R. J.; Molema, G.; Dings, R. P. Angiogenesis treatment, new concepts on the horizon. Angiogenesis 2006, 9, 67-72.
23. Starzec, A.; Vassy, R.; Martin, A.; Lecouvey, M.; Di Benedetto, M.; Crepin, M.; Perret, G. Y. Antiangiogenic and antitumor activities of peptide inhibiting the vascular endothelial growth factor binding to neuropilin-1. Life Sci. 2006, 79, 2370-2381.
24. Fong, T. A.; Shawver, L. K.; Sun, L.; Tang, C.; App, H.; Powell, T. J.; Kim, Y. H.; Schreck, R.; Wang, X.; Risau, W.; Ullrich, A.; Hirth, K. P.; McMahon, G. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res. 1999, 59, 99-106.
25. Dings, R. P.; Nesmelova, I.; Griffioen, A. W.; Mayo, K. H. Discovery and development of anti-angiogenic peptides: A structural link. Angiogenesis 2003, 6, 83-91.
26. Griffioen, A. W.; van der Schaft, D. W.; Barendsz-Janson, A. F.; Cox, A.; Struijker Boudier, H. A.; Hillen, H. F.; Mayo, K. H. Anginex, a designed peptide that inhibits angiogenesis. Biochem J. 2001, 354, 233-242.
27. Arroyo, M. M.; Mayo, K. H. NMR solution structure of the angiostatic peptide anginex. Biochem. Biophys. Acta, in press.
28. van der Schaft, D. W.; Dings, R. P.; de Lussanet, Q. G.; van Eijk, L. I.; Nap, A. W.; Beets-Tan, R. G.; Bouma-Ter Steege, J. C.; Wagstaff, J.; Mayo, K. H.; Griffioen, A. W. The designer anti-angiogenic peptide anginex targets tumor endothelial cells and inhibits tumor growth in animal models. FASEB J. 2002, 16, 1991-1993.
29. Dings, R. P.; van der Schaft, D. W.; Hargittai, B.; Haseman, J.; Griffioen, A. W.; Mayo, K. H. Anti-tumor activity of the novel angiogenesis inhibitor anginex. Cancer Lett. 2003, 194, 55-66.
30. Dings, R. P.; Yokoyama, Y.; Ramakrishnan, S.; Griffioen, A. W.; Mayo, K. H. The designed angiostatic peptide anginex synergistically improves chemotherapy and antiangiogenesis therapy with angiostatin. Cancer Res. 2003, 63, 382-385.
31. Dings, R. P.; Chen, X.; Hellebrekers, D. M.; van Eijk, L. I.; Zhang, Y.; Hoye, T. R.; Griffioen, A. W.; Mayo, K. H. Design of nonpeptidic topomimetics of antiangiogenic proteins with antitumor activities. J. Natl. Cancer Inst. 2006, 98, 932-936.
32. Dings, R. P.; Loren, M.; Heun, H.; McNiel, E.; Griffioen, A. W.; Mayo, K. H.; Griffin, R. J. Scheduling of radiation with angiogenesis inhibitors Anginex and Avastin improves therapeutic outcome via vessel normalization. Clin. Cancer Res. 2007, 13, 3395-3402.
33. Dings, R. P.; Williams, B. W.; Song, C. W.; Griffioen, A. W.; Mayo, K. H.; Griffin, R. J. Anginex synergizes with radiation therapy to inhibit tumor growth by radiosensitizing endothelial cells. Int. J. Cancer 2005, 115, 312-319.
34. Mayo, K. H.; Griffioen, A. W. Designing βpep Peptides: A Rational Approach to Discovery of Novel Pharmaceutical Agents and Small Molecules. Drugs Future 2003, 337-346.
35. Griffioen, A. W.; Damen, C. A.; Blijham, G. H.; Groenewegen, G. Tumor angiogenesis is accompanied by a decreased inflammatory response of tumor-associated endothelium. Blood 1996, 88, 667-673.
36. Tromp, S. C.; oude Egbrink, M. G.; Dings, R. P.; van Velzen, S.; Slaaf, D. W.; Hillen, H. F.; Tangelder, G. J.; Reneman, R. S.; Griffioen, A. W. Tumor angiogenesis factors reduce leukocyte adhesion in vivo. Int. Immunol. 2000, 12, 671-676.
37. Dirkx, A. E.; oude Egbrink, M. G.; Castermans, K.; van der Schaft, D. W.; Thijssen, V. L.; Dings, R. P.; Kwee, L.; Mayo, K. H.; Wagstaff, J.; Bouma-ter Steege, J. C.; Griffioen, A. W. Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. FASEB J. 2006, 20, 621-630.
38. Thijssen, V. L.; Postel, R.; Brandwijk, R. J.; Dings, R. P.; Nesmelova, I.; Satijn, S.; Verhofstad, N.; Nakabeppu, Y.; Baum, L. G.; Bakkers, J.; Mayo, K. H.; Poirier, F.; Griffioen, A. W. Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 15975-15980.
39. Barondes, S. H.; Castronovo, V.; Cooper, D. N.; Cummings, R. D.; Drickamer, K.; Feizi, T.; Gitt, M. A.; Hirabayashi, J.; Hughes, C.; Kasai, K. Galectins: a family of animal beta-galactoside-binding lectins. Cell 1994, 76, 597-598.
40. Rabinovich, G. A. Galectin-1 as a potential cancer target. Br. J. Cancer 2005, 92, 1188-1192.
41. Cao, Z.; Said, N.; Amin, S.; Wu, H. K.; Bruce, A.; Garate, M.; Hsu, D. K.; Kuwabara, I.; Liu, F. T.; Panjwani, N. Galectins-3 and -7, but not galectin-1, play a role in re-epithelialization of wounds. J. Biol. Chem. 2002, 277, 42299-42305.
42. Rubinstein, N.; Alvarez, M.; Zwirner, N. W.; Toscano, M. A.; Ilarregui, J. M.; Bravo, A.; Mordoh, J.; Fainboim, L.; Podhajcer, O. L.; Rabinovich, G. A. Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; A potential mechanism of tumor-immune privilege. Cancer Cells 2004, 5, 241-251.
43. Lotan, R.; Matsushita, Y.; Ohannesian, D.; Carralero, D.; Ota, D. M.; Cleary, K. R.; Nicolson, G. L.; Irimura, T. Lactose-binding lectin expression in human colorectal carcinomas. Relation to tumor progression. Carbohydr. Res. 1991, 213, 47-57.
44. Akerman, M. E.; Pilch, J.; Peters, D.; Ruoslahti, E. Angiostatic peptides use plasma fibronectin to home to angiogenic vasculature. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 2040-2045.
45. Gentilucci, L.; Cardillo, G.; Squassabia, F.; Tolomelli, A.; Spampinato, S.; Sparta, A.; Baiula, M. Inhibition of cancer cell adhesion by heterochiral Pro-containing RGD mimetics. Bioorg. Med. Chem. Lett., in press.
46. Maubant, S.; Saint-Dizier, D.; Boutillon, M.; Perron-Sierra, F.; Casara, P. J.; Hickman, J. A.; Tucker, G. C.; Van Obberghen-Schilling, E. Blockade of alpha v beta3 and alpha v beta5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells. Blood 2006, 108, 3035-3044.
47. Temming, K.; Schiffelers, R. M.; Molema, G.; Kok, R. J. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist. Updates 2005, 8, 381-402.
48. Reiher, F. K.; Volpert, O. V.; Jimenez, B.; Crawford, S. E.; Dinney, C. P.; Henkin, J.; Haviv, F.; Bouck, N. P.; Campbell, S. C. Inhibition of tumor growth by systemic treatment with thrombospondin-1 peptide mimetics. Int. J. Cancer 2002, 98, 682-689.
49. Markovic, S. N.; Suman, V. J.; Rao, R. A.; Ingle, J. N.; Kaur, J. S.; Erickson, L. A.; Pitot, H. C.; Croghan, G. A.; McWilliams, R. R.; Merchan, J.; Kottschade, L. A.; Nevala, W. K.; Uhl, C. B.; Allred, J.; Creagan, E. T. A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of metastatic melanoma. Am. J. Clin. Oncol. 2007, 30, 303-309.
50. Mochizuki, M.; Philp, D.; Hozumi, K.; Suzuki, N.; Yamada, Y.; Kleinman, H. K.; Nomizu, M. Angiogenic activity of syndecan-binding laminin peptide AG73 (RKRLQVQLSIRT). Arch. Biochem. Biophys. 2007, 459, 249-255.
51. Hozumi, K.; Suzuki, N.; Nielsen, P. K.; Nomizu, M.; Yamada, Y. Laminin alpha1 chain LG4 module promotes cell attachment through syndecans and cell spreading through integrin alpha2beta1. J. Biol. Chem. 2006, 281, 32929-32940.
52. Wickstrom, S. A.; Alitalo, K.; Keski-Oja, J. An endostatin-derived peptide interacts with integrins and regulates actin cytoskeleton and migration of endothelial cells. J. Biol. Chem. 2004, 279, 20178-20185.
53. Mulder, W. J.; van der Schaft, D. W.; Hautvast, P. A.; Strijkers, G. J.; Koning, G. A.; Storm, G.; Mayo, K. H.; Griffioen, A. W.; Nicolay, K. Early in vivo assessment of angiostatic therapy efficacy by molecular MRI. FASEB J. 2007, 21, 378-383.
54. de Lussanet, Q. G.; Beets-Tan, R. G.; Backes, W. H.; van der Schaft, D. W.; van Engelshoven, J. M.; Mayo, K. H.; Griffioen, A. W. Dynamic contrast-enhanced magnetic resonance imaging at 1.5 Tesla with gadopentetate dimeglumine to assess the angiostatic effects of anginex in mice. Eur. J. Cancer 2004, 40, 1262-1268.
55. Brandwijk, R. J.; Mulder, W. J.; Nicolay, K.; Mayo, K. H.; Thijssen, V. L.; Griffioen, A. W. Anginex-conjugated liposomes for targeting of angiogenic endothelial cells. Bioconjugate Chem. 2007, 18, 785-790.
56. Mayo, K. H.; Dings, R. P.; Flader, C.; Nesmelova, I.; Hargittai, B.; van der Schaft, D. W.; van Eijk, L. I.; Walek, D.; Haseman, J.; Hoye, T. R.; Griffioen, A. W. Design of a partial peptide mimetic of anginex with antiangiogenic and anticancer activity. J. Biol. Chem. 2003, 278, 45746-45752.
57. Dings, R. P.; Arroyo, M. M.; Lockwood, N. A.; Van Eijk, L. I.; Haseman, J. R.; Griffioen, A. W.; Mayo, K. H. Beta-sheet is the bioactive conformation of the anti-angiogenic anginex peptide. Biochem. J. 2003, 23, 281-288.
58. Kim, H. O.; Kahn, M. A merger of rational drug design and combinatorial chemistry: development and application of peptide secondary structure mimetics. Comb. Chem. High Throughput Screening 2000, 3, 167-183.
59. Tsang, K. Y.; Diaz, H.; Graciani, N.; Kelly, J. W. Hydrophobic cluster formation is necessary for dibezofuran-based amino acids to function as β-sheet nucleators. J. Am. Chem. Soc. 1994, 116, 3988-4005.
60. Blaskovich, M. A.; Lin, Q.; Delarue, F. L.; Sun, J.; Park, H. S.; Coppola, D.; Hamilton, A. D.; Sebti, S. M. Design of GFB-111, a platelet-derived growth factor binding molecule with antiangiogenic and anticancer activity against human tumors in mice. Nat. Biotechnol. 2000, 18, 1065-1070.
61. Sun, J.; Blaskovich, M. A.; Jain, R. K.; Delarue, F.; Paris, D.; Brem, S.; Wotoczek-Obadia, M.; Lin, Q.; Coppola, D.; Choi, K.; Mullan, M.; Hamilton, A. D.; Sebti, S. M. Blocking angiogenesis and tumorigenesis with GFA-116, a synthetic molecule that inhibits binding of vascular endothelial growth factor to its receptor. Cancer Res. 2004, 64, 3586-3592.
62. Sun, J.; Wang, D. A.; Jain, R. K.; Carie, A.; Paquette, S.; Ennis, E.; Blaskovich, M. A.; Baldini, L.; Coppola, D.; Hamilton, A. D.; Sebti, S. M. Inhibiting angiogenesis and tumorigenesis by a synthetic molecule that blocks binding of both VEGF and PDGF to their receptors. Oncogene 2005, 24, 4701-4709.
63. Creighton, C. J.; Du, Y.; Santulli, R. J.; Tounge, B. A.; Reitz, A. B. Synthesis and biological evaluation of type VI beta-turn templated RGD peptidomimetics. Bioorg. Med. Chem. Lett. 2006, 16, 3971-3974.
64. Athanassiou, Z.; Patora, K.; Dias, R. L.; Moehle, K.; Robinson, J. A.; Varani, G. Structure-guided peptidomimetic design leads to nanomolar beta-hairpin inhibitors of the Tat-TAR interaction of bovine immunodeficiency virus. Biochemistry 2007, 46, 741-751.
65. Hammond, M. C.; Harris, B. Z.; Lim, W. A.; Bartlett, P. A. Beta strand peptidomimetics as potent PDZ domain ligands. Chem. Biol. 2006, 13, 1247-1251.
66. Reichelt, A.; Martin, S. F. Synthesis and properties of cyclopropane-derived peptidomimetics. Acc. Chem. Res. 2006, 39, 433-442.
67. Fu, Y.; Xu, B.; Zou, X.; Ma, C.; Yang, X.; Mou, K.; Fu, G.; Lu, Y.; Xu, P. Design and synthesis of a novel class of furan-based molecules as potential 20S proteasome inhibitors. Bioorg. Med. Chem. Lett. 2007, 17, 1102-1106.
68. Dijkgraaf, I.; Kruijtzer, J. A.; Frielink, C.; Soede, A. C.; Hilbers, H. W.; Oyen, W. J.; Corstens, F. H.; Liskamp, R. M.; Boerman, O. C. Synthesis and biological evaluation of potent alphavbeta3-integrin receptor antagonists. Nucl. Med. Biol. 2006, 33, 953-961.
69. Palomo, C.; Aizpurua, J. M.; Balentova, E.; Jimenez, A.; Oyarbide, J.; Fratila, R. M.; Miranda, J. I. Synthesis of beta-lactam scaffolds for ditopic peptidomimetics. Org. Lett. 2007, 9, 101-104.
70. Baran, I.; Varekova, R. S.; Parthasarathi, L.; Suchomel, S.; Casey, F.; Shields, D. C. Identification of Potential Small Molecule Peptidomimetics Similar to Motifs in Proteins. J. Chem. Inf. Model., in press.
71. Berg, V.; Sellstedt, M.; Hedenstrom, M.; Pinkner, J. S.; Hultgren, S. J.; Almqvist, F. Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic 2-pyridones-targeting virulence of uropathogenic E. coli. Bioorg. Med. Chem. 2006, 14, 7563-7581.
72. Chen, X.; Dings, R. P.; Nesmelova, I.; Debbert, S.; Haseman, J. R.; Maxwell, J.; Hoye, T. R.; Mayo, K. H. Topomimetics of amphipathic beta-sheet and helix-forming bactericidal peptides neutralize lipopolysaccharide endotoxins. J. Med. Chem. 2006, 49, 7754-7765.
73. Clore, G. M.; Appella, E.; Yamada, M.; Matsushima, K.; Gronenborn, A. M. Three-dimensional structure of interleukin 8 in solution. Biochemistry 1990, 29, 1689-1696.
74. Gross, J. D.; Moerke, N. J.; von der Haar, T.; Lugovskoy, A. A.; Sachs, A. B.; McCarthy, J. E.; Wagner, G. Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E. Cell 2003, 115, 739-750.