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Identification of tissue-specific targeting peptide

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Abstract

Using phage display technique, we identified tissue-targeting peptide sets that recognize specific tissues (bone-marrow dendritic cell, kidney, liver, lung, spleen and visceral adipose tissue). In order to rapidly evaluate tissue-specific targeting peptides, we performed machine learning studies for predicting the tissue-specific targeting activity of peptides on the basis of peptide sequence information using four machine learning models and isolated the groups of peptides capable of mediating selective targeting to specific tissues. As a representative liver-specific targeting sequence, the peptide “DKNLQLH” was selected by the sequence similarity analysis. This peptide has a high degree of homology with protein ligands which can interact with corresponding membrane counterparts. We anticipate that our models will be applicable to the prediction of tissue-specific targeting peptides which can recognize the endothelial markers of target tissues.

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References

  1. Alley SC, Okeley NM, Senter PD (2010) Antibody-drug conjugates: targeted drug delivery for cancer. Curr Opin Chem Biol 14:529–537

    Article  CAS  Google Scholar 

  2. Vives E, Schmidt J, Pelegrin A (2008) Cell-penetrating and cell-targeting peptides in drug delivery. BBA Rev Cancer 1786:126–138

    CAS  Google Scholar 

  3. Ray P, White RR (2010) Aptamers for targeted drug delivery. Pharmaceuticals 3:1761–1778

    Article  CAS  Google Scholar 

  4. Singha R, Lillard JWM (2009) Nanoparticle-based targeted drug delivery. Exp Mol Pathol 86:215–223

    Article  Google Scholar 

  5. Pasqualini R, Ruoslahti E (1996) Organ targeting in vivo using phage display peptide libraries. Nature 380:364–366

    Article  CAS  Google Scholar 

  6. Rajotte D, Arap W, Hagedorn M, Koivunen E, Pasqualini R, Ruoslahti E (1998) Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display. J Clin Invest 102:430–437

    Article  CAS  Google Scholar 

  7. Trepel M, Arap W, Pasqualini R (2000) Exploring vascular heterogeneity for gene therapy targeting. Gene Ther 7:2059–2060

    Article  CAS  Google Scholar 

  8. William CA (2007) Phenotypic heterogeneity of the endothelium : I. Structure, function, and mechanisms. Circ Res 100:158–173

    Article  Google Scholar 

  9. William CA (2007) Phenotypic heterogeneity of the endothelium. Circ Res 100:174–190

    Article  Google Scholar 

  10. Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279:377–380

    Article  CAS  Google Scholar 

  11. Kolonin MG, Pasqualini R, Arap W (2001) Molecular addresses in blood vessels as targets for therapy. Curr Opin Chem Biol 5:308–313

    Article  CAS  Google Scholar 

  12. Arap W, Haedicke W, Bernasconi M, Kain R, Rajotte D, Krajewski S, Ellerby HM, Bredesen DE, Pasqualini R, Ruoslahti E (2002) Targeting the prostate for destruction through a vascular address. Proc Natl Acad Sci USA 99:1527–1531

    Article  CAS  Google Scholar 

  13. Durr E, Yu J, Krasinska KM, Carver LA, Yates JR, Testa JE, Oh P, Schnitzer JE (2004) Direct proteomic mapping of the lung microvascular endothelial cell surface in vivo and in cell culture. Nat Biotechnol 22:985–992

    Article  CAS  Google Scholar 

  14. Oh P, Li Y, Yu J, Durr E, Krasinska K, Carver LA, Testa JE, Schnitzer JE (2004) Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy. Nature 429:629–635

    Article  CAS  Google Scholar 

  15. Majumdar S, Siahaan TJ (2010) Peptide-mediated targeted drug delivery. Med Res Rev. doi:10.1002/med.20225

    Google Scholar 

  16. Binétruy-Tournaire R, Demangel C, Malavaud B, Vassy R, Rouyre S, Kraemer M, Plouët J, Derbin C, Perret G, Mazié JC (2000) Identification of a peptide blocking vascular endothelial growth factor(VEGF)-mediated angiogenesis. EMBO J 19:1525–1533

    Article  Google Scholar 

  17. Askoxylakis V, Zitzmann S, Mier W, Graham K, Krämer S, von Wegner F, Fink RH, Schwab M, Eisenhut M, Haberkorn U (2005) Preclinical evaluation of the breast cancer cell-binding peptide, p160. Clin Cancer Res 11:6705–6712

    Article  CAS  Google Scholar 

  18. Zang L, Shi L, Guo J, Pan Q, Wu W, Pan X, Wang J (2009) Screening and identification of a peptide specifically targeted to NCI-H1299 from a phage display peptide library. Cancer Lett 281:64–70

    Article  CAS  Google Scholar 

  19. Yanofsky SD, Baldwin DN, Butler JH, Holden FR, Jacobs JW, Balasubramanian P, Chinn JP, Cwirla SE, Peters-Bhatt E, Whitehorn EA, Tate EH, Akeson A, Bowlin TL, Dower WJ, Barrett RW (1996) High affinity type I interleukin 1 receptor antagonists discovered by screening recombinant peptide libraries. Proc Natl Acad Sci USA 93:7381–7386

    Article  CAS  Google Scholar 

  20. Tian W, Bai G, Li ZH, Yang WB (2006) Antagonist peptides of human interferon-alpha2b isolated from phage display library inhibit interferon induced antiviral activity. Acta Pharmacol Sin 27:1044–1050

    Article  Google Scholar 

  21. Kang SK, Woo JH, Kim MK, Woo SS, Choi JH, Lee HG, Lee NK, Choi YJ (2008) Identification of a peptide sequence that improves transport of macromolecules across the intestinal mucosal barrier targeting goblet cells. J Biotechnol 135:210–216

    Article  CAS  Google Scholar 

  22. Chen Y, Shen Y, Guo X, Zhang C, Yang W, Ma M, Liu S, Zhang M, Wen LP (2006) Transdermal protein delivery by a coadministered peptide identified via phage display. Nat Biothechnol 24:455–460

    Article  CAS  Google Scholar 

  23. Wan XM, Chen YP, Xu WR, Yang WJ, Wen LP (2009) Identification of nose-to-brain homing peptide through phage display. Peptides 30:343–350

    Article  CAS  Google Scholar 

  24. Zhang L, Hoffman JA, Ruoslahti E (2005) Molecular profiling of heart endothelial cells. Circulation 112:1601–1611

    Article  CAS  Google Scholar 

  25. Pasqualini R, Koivunen E, Ruoslahti E (1997) Alpha v integrins as receptors for tumor targeting by circulating ligands. Nat Biotechnol 15:542–546

    Article  CAS  Google Scholar 

  26. Burg MA, Pasqualini R, Arap W, Ruoslahti E, Stallcup WB (1999) NG2 proteoglycan-binding peptides target tumor neovasculature. Cancer Res 59:2869–2874

    CAS  Google Scholar 

  27. Laakkonen P, Akerman ME, Biliran H, Yang M, Ferrer F, Karpanen T, Hoffman RM, Ruoslahti E (2004) Antitumor activity of a homing peptide that targets tumor lymphatics and tumor cells. Proc Natl Acad Sci USA 101:9381–9386

    Article  CAS  Google Scholar 

  28. Arap W, Kolonin MG, Trepel M, Lahdenranta J, Cardó-Vila M, Giordano RJ, Mintz PJ, Ardelt PU, Yao VJ, Vidal CI, Chen L, Flamm A, Valtanen H, Weavind LM, Hicks ME, Pollock RE, Botz GH, Bucana CD, Koivunen E, Cahill D, Troncoso P, Baggerly KA, Pentz RD, Do KA, Logothetis CJ, Pasqualini R (2002) Steps toward mapping the human vasculature by phage display. Nat Med 8:121–127

    Article  CAS  Google Scholar 

  29. Ellerby HM, Arap W, Ellerby LM, Kain R, Andrusiak R, Rio GD, Krajewski S, Lombardo CR, Rao R, Ruoslahti E. Bredesen DE, Pasqualini R (1999) Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med 5:1032–1038

    Google Scholar 

  30. Chen Y, Xu X, Hong S, Chen J, Liu N, Underhill CB, Creswell K, Zhang L (2001) RGD-tachyplesin inhibits tumor growth. Cancer Res 61:2434–2438

    CAS  Google Scholar 

  31. Yoneda Y, Steiniger SC, Capková K, Mee JM, Liu Y, Kaufmann GF, Janda KD (2008) A cell-penetrating peptidic GRP78 ligand for tumor cell-specific prodrug therapy. Bioorg Med Chem Lett 18:1632–1636

    Article  CAS  Google Scholar 

  32. Curnis F, Sacchi A, Borgna L, Magni F, Gasparri A, Corti A (2000) Enhancement of tumor necrosis factor α antitumor immunotherapeutic properties by targeted delivery to aminopeptidase N (CD13). Nat Biotechnol 18:1185–1190

    Article  CAS  Google Scholar 

  33. Curnis F, Arrigoni G, Sacchi A, Fischetti L, Arap W, Pasqualini R, Corti A (2002) Differential binding of drugs containing the NGR motif to CD13 isoforms in tumor vessels, epithelia, and myeloid cells. Cancer Res 62:867–874

    CAS  Google Scholar 

  34. Jung E, Kim J, Kim M, Jung DH, Rhee H, Shin JM, Choi K, Kang SK, Kim MK, Yun CH, Choi YJ, Choi SH (2007) Artificial neural network models for prediction of intestinal permeability of oligopeptides. BMC Bioinformat 8:245

    Article  Google Scholar 

  35. Jung E, Kim J, Choi SH, Kim M, Rhee H, Shin JM, Choi K, Kang SK, Lee NK, Choi YJ, Jung DH (2010) Artificial neural network study on organ-targeting peptides. J Comput Aided Mol Des 24:49–56

    Article  CAS  Google Scholar 

  36. Jung E, Choi SH, Lee NK, Kang SK, Choi YJ, Shin JM, Choi K, Jung DH (2011) Machine learning study for the prediction of transdermal peptide. J Comput Aided Mol Des 25:339–347

    Article  CAS  Google Scholar 

  37. Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM (1992) Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med 176:1693–1702

    Article  CAS  Google Scholar 

  38. Shepherd DM, Steppan LB, Hedstrom OR, Kerkvliet NI (2001) Anti-CD40 treatment of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed C57BL/6 mice induces activation of antigen presenting cells yet fails to overcome TCDD-induced suppression of allograft immunity. Toxicol Appl Pharmacol 170:10–22

    Article  CAS  Google Scholar 

  39. McCaldon P, Argos P (1988) Proteins 4:99–122

    Article  CAS  Google Scholar 

  40. Mei H, Lian ZH, Zhou Y, Li SZ (2005) A new set of amino acid descriptors and its application in peptide QSARs. Biopolymer (Peptide Science) 80:775–786

    Article  CAS  Google Scholar 

  41. Pipeline Pilot 8.0 (http://accelrys.com/products/pipeline-pilot/)

  42. The R Project for Statistical Computing (http://www.r-project.org/)

  43. Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143:29–36

    CAS  Google Scholar 

  44. Discovery Studio 3.1 (http://accelrys.com/products/discovery-studio/)

  45. Henikoff S, Henikoff JG (1992) Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci USA 89:10915–10919

    Article  CAS  Google Scholar 

  46. Gauthier MA, Klok HA (2008) Peptide/protein–polymer conjugates: synthetic strategies and design concepts. Chem Commun 23:2591–2611

    Article  Google Scholar 

  47. Molek P, Strukelj B, Bratkovic T (2011) Peptide phage display as a tool for drug discovery: targeting membrane receptors. Molecules 16:857–887

    Article  CAS  Google Scholar 

  48. Rajotte D, Ruoslahti E (1999) Membrane dipeptidase is the receptor for a lung-targeting peptide identified by in vivo phage display. J Biol Chem 274:11593–11598

    Article  CAS  Google Scholar 

  49. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W (2004) Reversal of obesity by targeted ablation of adipose tissue. Nat Med 10:625–632

    Article  CAS  Google Scholar 

  50. Bhattacharya SK, Peachey NS, Crabb JW (2005) Cochlin and glaucoma: a mini-review. Vis Neurosci 22:605–613

    Article  Google Scholar 

  51. Tuma PL, Hubbard AL (2003) Transcytosis: crossing cellular barriers. Physiol Rev 83:871–932

    CAS  Google Scholar 

  52. Favier B, Alam A, Barron P, Bonnin J, Laboudie P, Fons P, Mandron M, Herault JP, Neufeld G, Savi P, Herbert JM, Bono F (2006) Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cell survival and migration. Blood 108:1243–1250

    Article  CAS  Google Scholar 

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Acknowledgments

This research is supported by National Research Foundation of Korea (NRF), Korea government (MEST) (Project No. 2011-0029416). We thank Accelrys Korea for the support of SciTegic Pipeline Pilot and Discovery Studio software, and acknowledge the assistance of BioMedES (http://www.biomedes.co.uk/home).

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Authors and Affiliations

  1. Insilicotech Co. Ltd., C-602 Korea Bio Park, 694-1, Sampyeong, Bundang-Gu, Seongnam-Shi, 463-400, Korea

    Eunkyoung Jung, Seung-Hoon Choi, Daejin Kim, Kisoo Park & Dong Hyun Jung

  2. School of Agriculture Biotechnology, Seoul National University, San 56-1, Shilim-Dong, Kwanak-gu, Seoul, 151-742, Korea

    Nam Kyung Lee, Sang-Kee Kang & Yun-Jaie Choi

  3. Department of Chemistry, Korea University, 1, Anam-dong 5-Ga, Seongbuk-Gu, Seoul, 136-701, Korea

    Kihang Choi

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  1. Eunkyoung Jung
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Correspondence to Dong Hyun Jung.

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Jung, E., Lee, N.K., Kang, SK. et al. Identification of tissue-specific targeting peptide. J Comput Aided Mol Des 26, 1267–1275 (2012). https://doi.org/10.1007/s10822-012-9614-6

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  • DOI: https://doi.org/10.1007/s10822-012-9614-6

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