Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity

PLoS ONE

Volumn 8, Issue 11, 2013, Pages

  Han, Xiaofeng ^a   Xu, Yan ^a   Yang, Yilei ^a   Xi, Jingle ^a,b   Tian, Wang ^a   Duggineni, Srinivas ^a   Huang, Ziwei ^a   An, Jing ^a  

^a State University of New York Upstate Medical University: College of Medicine   (United States)

^b SOUTHERN MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPEPTIDE; CYSTEINYLTHREONYLTYROSYLTYROSYLTRYPTOPYLPROLYLLEUCYLPROLYLCYSTEINE; EPHRIN A5; EPHRIN RECEPTOR A4; NONAPEPTIDE; UNCLASSIFIED DRUG;

ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG CYTOTOXICITY; HUMAN; HUMAN CELL; MOLECULAR DOCKING; NERVE CELL DIFFERENTIATION; PHAGE DISPLAY; PROTEIN ANALYSIS; PROTEIN INTERACTION; PROTEIN SYNTHESIS INHIBITION; RECEPTOR BINDING;

AMINO ACID SEQUENCE; ANGIOGENESIS INHIBITORS; BINDING SITES; CELL SURVIVAL; EPHRINS; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; LIGANDS; MOLECULAR DOCKING SIMULATION; NEOVASCULARIZATION, PHYSIOLOGIC; PEPTIDES, CYCLIC; PROTEIN BINDING; PROTEIN CONFORMATION; RECEPTOR, EPHA4;

EID: 84893055271     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0080183     Document Type: Article

References (34)

1. Castaño J, Davalos V, Schwartz S Jr., Arango D (2008) EPH receptors in cancer. Histol Histopathol 23: 1011-1023. PubMed: 18498077.
2. Brantley-Sieders D, Schmidt S, Parker M, Chen J (2004) Eph receptor tyrosine kinases in tumor and tumor microenvironment. Curr Pharm Des 10: 3431-3442. doi:10.2174/1381612043383160. PubMed: 15544526.
3. Pasquale EB (2005) Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 6: 462-475. doi:10.1038/nrm1662. PubMed: 15928710.
4. Murai KK, Pasquale EB (2003) 'Eph'ective signaling: forward, reverse and crosstalk. J Cell Sci 116: 2823-2832.
5. Palmer A, Klein R (2003) Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function Genes Dev 17: 1429-1450. doi:10.1101/gad.1093703. PubMed: 12815065.
6. Mosch B, Reissenweber B, Neuber C, Pietzsch J (2010) Eph receptors and ephrin ligands: important players in angiogenesis and tumor angiogenesis. J Oncol 135285: 1-12 PubMed: 20224755.
7. Du J, Fu C, Sretavan DW (2007) Eph/ephrin signaling as a potential therapeutic target after central nervous system injury Curr Pharm Des 13: 2507-2518. doi:10.2174/138161207781368594. PubMed: 17692019.
8. Walkenhorst J, Dütting D, Handwerker C, Huai J, Tanaka H et al. (2000) The EphA4 receptor tyrosine kinase is necessary for the guidance of nasal retinal ganglion cell axons in vitro. Mol Cell Neurosci 16: 365-375. doi:10.1006/mcne.2000.0878. PubMed: 11085874.
9. Goldshmit Y, Spanevello MD, Tajouri S, Li L, Rogers F et al. (2011) EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice. PLOS ONE 6: e24636. doi:10.1371/journal.pone.0024636. PubMed: 21931787.
10. Munro KM, Perreau VM, Turnley AM (2012) Differential gene expression in the EphA4 knockout spinal cord and analysis of the inflammatory response following spinal cord injury. PLOS ONE 7: 1-13. PubMed: 22629434.
11. Li J, Liu N, Wang Y, Wang R, Guo D et al. (2012) Inhibition of EphA4 signaling after ischemia-reperfusion reduces apoptosis of CA1 pyramidal neurons. Neurosci Lett 518: 92-95. doi:10.1016/j.neulet.2012.04.060. PubMed: 22580205.
12. Fabes J, Anderson P, Brennan C, Bolsover S (2007) Regeneration-enhancing effects of EphA4 blocking peptide following corticospinal tract injury in adult rat spinal cord. Eur J Neurosci 26: 2496-2505. doi:10.1111/j.1460-9568.2007. 05859.x. PubMed: 17970742.
13. Van Hoecke A, Schoonaert L, Lemmens R, Timmers M, Staats KA et al. (2012) EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans. Nat Med 18: 1418-1422. doi:10.1038/nm.2901. PubMed: 22922411.
14. Fabes J, Anderson P, Brennan C, Bolsover S (2007) Regeneration-enhancing effects of EphA4 blocking peptide following corticospinal tract injury in adult rat spinal cord. Eur J Neurosci 26: 2496-2505. doi:10.1111/j.1460-9568.2007. 05859.x. PubMed: 17970742.
15. Goldshmit Y, Galea MP, Wise G, Bartlett PF, Turnley AM (2004) Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice. J Neurosci 24: 10064-10073. doi:10.1523/JNEUROSCI.2981-04.2004. PubMed: 15537875.
16. van Doorn R, Dijkman R, Vermeer MH, Out-Luiting JJ, van der Raaij-Helmer EM et al. (2004) Aberrant expression of the tyrosine kinase receptor EphA4 and the transcription factor twist in Sezary syndrome identified by gene expression analysis. Cancer Res 64: 5578-5586. doi:10.1158/0008-5472.CAN-04-1253. PubMed: 15313894.
17. Iiizumi M, Hosokawa M, Takehara A, Chung S, Nakamura T et al. (2006) EphA4 receptor, overexpressed in pancreatic ductal adenocarcinoma, promotes cancer cell growth. Cancer Sci 97: 1211-1216. doi:10.1111/j.1349-7006.2006. 00313.x. PubMed: 16965393.
18. Oki M, Yamamoto H, Taniguchi H, Adachi Y, Imai K et al. (2008) Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers. World J Gastroenterol 14: 5650-5656. doi:10.3748/wjg.14.5650. PubMed: 18837080.
19. Ashida S, Nakagawa H, Katagiri T, Furihata M, Iiizumi M et al. (2004) Molecular features of the transition from prostatic intraepithelial neoplasia (PIN) to prostate cancer: genome-wide gene-expression profiles of prostate cancers and PINs. Cancer Res 64: 5963-5972. doi:10.1158/0008-5472.CAN-04-0020. PubMed: 15342375.
20. Brantley-Sieders DM, Jiang A, Sarma K, Badu-Nkansah A, Walter DL et al. (2011) Eph/ephrin profiling in human breast cancer reveals significant associations between expression level and clinical outcome. PLOS ONE 6: e24426. doi:10.1371/journal.pone.0024426. PubMed: 21935409.
21. Oki M, Yamamoto H, Taniguchi H, Adachi Y, Imai K et al. (2008) Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers. World J Gastroenterol, 14: 5650-5656. PubMed: 18837080.
22. Sawada T, Jing X, Zhang Y, Shimada E, Yokote H et al. (2010) Ternary complex formation of EphA4, FGFR and FRS2alpha plays an important role in the proliferation of embryonic neural stem/progenitor cells. Genes Cells 15: 297-311. doi:10.1111/j.1365-2443.2010.01391.x. PubMed: 20184660.
23. Fukai J, Yokote H, Yamanaka R, Arao T, Nishio K et al. (2008) EphA4 promotes cell proliferation and migration through a novel EphA4-FGFR1 signaling pathway in the human glioma U251 cell line. Mol Cancer Ther 7: 2768-2778. doi:10.1158/1535-7163.MCT-07-2263. PubMed: 18790757.
24. Pasquale EB (2010) Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 10: 165-180. doi:10.1038/nrc2806. PubMed: 20179713.
25. Murai KK, Nguyen LN, Koolpe M, McLennan R, Krull CE et al. (2003) Targeting the EphA4 receptor in the nervous system with biologically active peptides. Mol Cell Neurosci 24: 1000-1011. doi:10.1016/j.mcn.2003.08.006. PubMed: 14697664.
26. Koolpe M, Burgess R, Dail M, Pasquale EB (2005) EphB receptor-binding peptides identified by phage display enable design of an antagonist with ephrin-like affinity. J Biol Chem 280: 17301-17311. doi:10.1074/jbc.M500363200. PubMed: 15722342.
27. Koolpe M, Dail M, Pasquale EB (2002) An ephrin mimetic peptide that selectively targets the EphA2 receptor. J Biol Chem 277: 46974-46979. doi:10.1074/jbc.M208495200. PubMed: 12351647.
28. Noberini R, Koolpe M, Peddibhotla S, Dahl R, Su Y et al. (2008) Small molecules can selectively inhibit ephrin binding to the EphA4 and EphA2 receptors. J Biol Chem 283: 29461-29472. doi:10.1074/jbc.M804103200. PubMed: 18728010.
29. Horswill AR, Benkovic SJ (2005) Cyclic peptides, a chemical genetics tool for biologists. Cell Cycle 4: 552-555. doi:10.4161/cc.4.4.1585. PubMed: 15876867.
30. Young TS, Young DD, Ahmad I, Louis JM, Benkovic SJ et al. (2011) Evolution of cyclic peptide protease inhibitors. Proc Natl Acad Sci U S A 108: 11052-11056. doi:10.1073/pnas.1108045108. PubMed: 21690365.
31. Xi J, Zhu X, Feng Y, Huang N, Luo G et al. (2013) A novel class of tubulin inhibitors with promising anticancer activities. Mol Cancer Res 11: 856-864. doi:10.1158/1541-7786.MCR-12-0177. PubMed: 23666368.
32. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE et al. (1998) Automated Docking Using a Lamarkian Genetic Algorithm and Empirical Binding Free Energy Function. J Comput Chem 19: 1639-1662. doi:10.1002/(SICI)1096- 987X(19981115)19:14.
33. SYBYL-X1.3 Tripos International (1699) South Hanley Rd. St Louis MO, 63144, USA
34. Bowden TA, Aricescu AR, Nettleship JE, Siebold C, Rahman-Huq N et al. (2009) Structural plasticity of eph receptor A4 facilitates cross-class ephrin signaling. Structure 17: 1386-1397. doi:10.1016/j.str.2009.07.018. PubMed: 19836338.