Application of Cell Penetrating Peptides for Intracellular Delivery of Endostatin: A Computational Approach


Дәйексөз келтіру

Толық мәтін

Аннотация

Background:Endostatin is an antiangiogenic compound with anticancer activity. The poor stability and low half-life of endostatin are the main barriers to the clinical use of this protein. Cell-penetrating peptides (CPPs) are extensively applied as carrier in the delivery of drugs and different therapeutic agents. Therefore, they can be proper candidates to improve endostatin delivery to the target cells.

Objective:In this study, we aim to computationally predict appropriate CPPs for the delivery of endostatin.

Methods:Potential appropriate CPPs for protein delivery were selected based on the literature. The main parameters for detection of best CPP-endostatin fusions, including stability, hydrophobicity, antigenicity, and subcellular localization, were predicted using ProtParam, VaxiJen, and DeepLoc-1.0 servers, respectively. The 3D structures of the best CPP-Endostatin fusions were modeled by the I-TASSER server. The predicted models were validated using PROCHECK, ERRAT, Verify3D and ProSA-Web servers. The best models were visualized by the PyMol molecular graphics system.

Results:Considering the principal parameters in the selection of best CPPs for endostatin delivery, endostatin fusions with four CPPs, including Cyt c-ss-MAP, TP-biot1, MPGα, and DPV1047, high stability and hydrophobicity, no antigenicity and extracellular localization were predicted as the best potential fusions for endostatin delivery. Four CPPs, including Cyt c-ss-MAP, TP-biot1, MPGα, and DPV1047, were predicted as the best potential candidates to improve endostatin delivery.

Conclusion:Application of these CPPs may overcome the limitation of endostatin therapeutic applications, including poor stability and low half-life. Subsequent experimental studies will contribute to verifying these computational results.

Авторлар туралы

Mozhdeh Zamani

Autophagy Research Center, Shiraz University of Medical Sciences

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Navid Nezafat

Pharmaceutical Sciences Research Cente, Shiraz University of Medical Sciences

Email: info@benthamscience.net

Pooneh Mokarram

Department of Biochemistry, Autophagy Research Center, School of Medicine, Shiraz University of Medical Sciences

Email: info@benthamscience.net

Behnam Kadkhodaei

Department of Radiation Oncology,, Shiraz University of Medical Sciences

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Әдебиет тізімі

  1. Habault, J.; Poyet, J.L. Recent advances in cell penetrating peptide-based anticancer therapies. Molecules, 2019, 24(5), 927. doi: 10.3390/molecules24050927 PMID: 30866424
  2. Teleanu, R.I.; Chircov, C.; Grumezescu, A.M.; Teleanu, D.M. Tumor angiogenesis and anti-angiogenic strategies for cancer treatment. J. Clin. Med., 2019, 9(1), 84. doi: 10.3390/jcm9010084 PMID: 31905724
  3. Wu, T.; Duan, X.; Hu, T.; Mu, X.; Jiang, G.; Cui, S. Effect of endostatin on Wnt pathway of stem-like cells in bladder cancer in tumor microenvironment. Mol. Biol. Rep., 2020, 47(5), 3937-3948. doi: 10.1007/s11033-020-05487-3 PMID: 32388699
  4. Hua, L.; Ping, L.; Hong-Yan, G. Recent advances on the modified endostatin and ocular neovascularization. Int. J. Ophthalmol., 2009, 2(4), 642-644.
  5. Mohajeri, A.; Sanaei, S.; Kiafar, F.; Fattahi, A.; Khalili, M.; Zarghami, N. The challenges of recombinant endostatin in clinical application: Focus on the different expression systems and molecular bioengineering. Adv. Pharm. Bull., 2017, 7(1), 21-34. doi: 10.15171/apb.2017.004 PMID: 28507934
  6. Poluzzi, C.; Iozzo, R.V.; Schaefer, L. Endostatin and endorepellin: A common route of action for similar angiostatic cancer avengers. Adv. Drug Deliv. Rev., 2016, 97, 156-173. doi: 10.1016/j.addr.2015.10.012 PMID: 26518982
  7. Ramakrishnan, S.; Bui Nguyen, T.M.; Subramanian, I.V.; Kelekar, A. Autophagy and angiogenesis inhibition. Autophagy, 2007, 3(5), 511-514. doi: 10.4161/auto.4734 PMID: 17643071
  8. Nguyen, T.M.B.; Subramanian, I.V.; Xiao, X.; Ghosh, G.; Nguyen, P.; Kelekar, A.; Ramakrishnan, S. Endostatin induces autophagy in endothelial cells by modulating Beclin 1 and β-catenin levels. J. Cell. Mol. Med., 2009, 13(9b), 3687-3698. doi: 10.1111/j.1582-4934.2009.00722.x PMID: 19298526
  9. Li, K.; Shi, M.; Qin, S. Current status and study progress of recombinant human endostatin in cancer treatment. Oncol. Ther., 2018, 6(1), 21-43. doi: 10.1007/s40487-017-0055-1 PMID: 32700135
  10. Ren, Z.; Wang, Y.; Jiang, W.; Dai, W.; Jiang, Y. Anti-tumor effect of a novel soluble recombinant human endostatin: administered as a single agent or in combination with chemotherapy agents in mouse tumor models. PLoS One, 2014, 9(9), e107823. doi: 10.1371/journal.pone.0107823 PMID: 25229620
  11. Wang, Z.Q.; Wang, D.S.; Wang, F.H.; Ren, C.; Tan, Q.; Li, Y.H. Recombinant human endostatin plus paclitaxel/nedaplatin for recurrent or metastatic advanced esophageal squamous cell carcinoma: A prospective, single-arm, open-label, phase II study. Invest. New Drugs, 2021, 39(2), 516-523. doi: 10.1007/s10637-020-01021-1 PMID: 33070249
  12. Chen, L.; Shi, H.; Che, Y.; Sun, W.; Niu, X.; Lu, W. Verification of protein structures: Patterns of nonbonded atomic interactions transcatheter arterial infusion and chemoembolization on gastric cancer with liver metastasis and analysis of prognosis. J. BUON, 2020, 25, 1469-1475. PMID: 32862592
  13. Hai-Tao, Z.; Hui-Cheng, L.; Zheng-Wu, L.; Chang-Hong, G. A tumor-penetrating peptide modification enhances the antitumor activity of endostatin in vivo. Anticancer Drugs, 2011, 22(5), 409-415. doi: 10.1097/CAD.0b013e328342050d PMID: 21427563
  14. Lee, T.Y.; Tjin Tham Sjin, R.M.; Movahedi, S.; Ahmed, B.; Pravda, E.A.; Lo, K.M.; Gillies, S.D.; Folkman, J.; Javaherian, K. Linking antibody Fc domain to endostatin significantly improves endostatin half-life and efficacy. Clin. Cancer Res., 2008, 14(5), 1487-1493. doi: 10.1158/1078-0432.CCR-07-1530 PMID: 18316573
  15. Guo, L.; Xu, B.; Zhou, D.; Chang, G.; Fu, Y.; Liu, L.; Luo, Y. Biophysical and biological characterization of PEGylated recombinant human endostatin. Clin. Exp. Pharmacol. Physiol., 2019, 46(10), 920-927. doi: 10.1111/1440-1681.13134 PMID: 31278773
  16. Tan, H.; Yang, S.; Feng, Y.; Liu, C.; Cao, J.; Mu, G.; Wang, F. Characterization and secondary structure analysis of endostatin covalently modified by polyethylene glycol and low molecular weight heparin. J. Biochem., 2008, 144(2), 207-213. doi: 10.1093/jb/mvn060 PMID: 18463113
  17. Jing, Y.; Lu, H.; Wu, K.; Subramanian, I.V.; Ramakrishnan, S. Inhibition of ovarian cancer by RGD-P125A-endostatin-Fc fusion proteins. Int. J. Cancer, 2011, 129(3), 751-761. doi: 10.1002/ijc.25932 PMID: 21225621
  18. Idiiatullina, E.; Al-Azab, M.; Walana, W.; Pavlov, V.; Liu, B. EnDuo, a novel derivative of Endostar, inhibits the migration of colon cancer cells, suppresses matrix metalloproteinase-2/9 expression and impedes AKT/ERK activation. Biomed. Pharmacother., 2021, 134, 111136. doi: 10.1016/j.biopha.2020.111136 PMID: 33341042
  19. Lindgren, M.; Hällbrink, M.; Prochiantz, A.; Langel, Ü. Cell-penetrating peptides. Trends Pharmacol. Sci., 2000, 21(3), 99-103. doi: 10.1016/S0165-6147(00)01447-4 PMID: 10689363
  20. Milletti, F. Cell-penetrating peptides: Classes, origin, and current landscape. Drug Discov. Today, 2012, 17(15-16), 850-860. doi: 10.1016/j.drudis.2012.03.002 PMID: 22465171
  21. Derossi, D.; Joliot, A.H.; Chassaing, G.; Prochiantz, A. The third helix of the Antennapedia homeodomain translocates through biological membranes. J. Biol. Chem., 1994, 269(14), 10444-10450. doi: 10.1016/S0021-9258(17)34080-2 PMID: 8144628
  22. Kardani, K.; Bolhassani, A. CPPsite 2.0: An available database of experimentally validated cell-penetrating peptides predicting their secondary and tertiary structures. J. Mol. Biol., 2021, 433(11), 166703. doi: 10.1016/j.jmb.2020.11.002 PMID: 33186582
  23. Zarei, M.; Rahbar, M.R.; Negahdaripour, M.; Morowvat, M.H.; Nezafat, N.; Ghasemi, Y. Cell penetrating peptide: Sequence-based computational prediction for intercellular delivery of arginine deiminase. Curr. Proteomics, 2020, 17(2), 117-131. doi: 10.2174/1570164616666190701120351
  24. Pundir, S.; Martin, M.J.; O’Donovan, C. UniProt Protein Knowledgebase. In: Protein bioinformatics. Methods in molecular biology; Wu, C.; Arighi, C.; Ross, K., Eds.; Humana Press: New York, NY, 2017; pp. 41-55. doi: 10.1007/978-1-4939-6783-4_2
  25. Gautam, A.; Chaudhary, K.; Kumar, R.; Raghava, G.P.S. Computer-aided virtual screening and designing of cell-penetrating peptides. Methods Mol. Biol., 2015, 1324, 59-69. doi: 10.1007/978-1-4939-2806-4_4
  26. Gasteiger, E.; Hoogland, C.; Gattiker, A.; Wilkins, M.R.; Appel, R.D.; Bairoch, A. Protein Identification and Analysis Tools on the ExPASy Server. In: The proteomics protocols handbook The proteomics protocols handbook; Springer Protocols Handbooks, 2005; pp. 571-607. doi: 10.1385/1-59259-890-0:571
  27. Doytchinova, I.A.; Flower, D.R. VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics, 2007, 8(1), 4. doi: 10.1186/1471-2105-8-4 PMID: 17207271
  28. Almagro Armenteros, J.J.; Sønderby, C.K.; Sønderby, S.K.; Nielsen, H.; Winther, O. DeepLoc: Prediction of protein subcellular localization using deep learning. Bioinformatics, 2017, 33(21), 3387-3395. doi: 10.1093/bioinformatics/btx431 PMID: 29036616
  29. Yang, J.; Yan, R.; Roy, A.; Xu, D.; Poisson, J.; Zhang, Y. The I-TASSER Suite: Protein structure and function prediction. Nat. Methods, 2015, 12(1), 7-8. doi: 10.1038/nmeth.3213 PMID: 25549265
  30. Laskowski, R.; MacArthur, M.; Thornton, J. PROCHECK: Validation of Protein-Structure Coordinates. In: Crystallography of biological macromolecules; , 2006. doi: 10.1107/97809553602060000882
  31. Colovos, C.; Yeates, T.O. Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Sci., 1993, 2(9), 1511-1519. doi: 10.1002/pro.5560020916 PMID: 8401235
  32. Lüthy, R.; Bowie, J.U.; Eisenberg, D. Assessment of protein models with three-dimensional profiles. Nature, 1992, 356(6364), 83-85. doi: 10.1038/356083a0 PMID: 1538787
  33. Wiederstein, M.; Sippl, M.J. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res., 2007, 35(S2), W407-W410. doi: 10.1093/nar/gkm290 PMID: 17517781
  34. Li, Y.; Rosal, R.V.; Brandt-Rauf, P.W.; Fine, R.L. Correlation between hydrophobic properties and efficiency of carrier-mediated membrane transduction and apoptosis of a p53 C-terminal peptide. Biochem. Biophys. Res. Commun., 2002, 298(3), 439-449. doi: 10.1016/S0006-291X(02)02470-1 PMID: 12413961
  35. Nam, S.H.; Park, J.; Koo, H. Recent advances in selective and targeted drug/gene delivery systems using cell-penetrating peptides. Arch. Pharm. Res., 2023, 46(1), 18-34. doi: 10.1007/s12272-022-01425-y PMID: 36593377
  36. Yokoyama, Y.; Ramakrishnan, S. Improved biological activity of a mutant endostatin containing a single amino-acid substitution. Br. J. Cancer, 2004, 90(8), 1627-1635. doi: 10.1038/sj.bjc.6601745 PMID: 15083196
  37. Xu, X.; Mao, W.; Chen, Q.; Zhuang, Q.; Wang, L.; Dai, J.; Wang, H.; Huang, Z. Endostar, a modified recombinant human endostatin, suppresses angiogenesis through inhibition of Wnt/β-catenin signaling pathway. PLoS One, 2014, 9(9), e107463. doi: 10.1371/journal.pone.0107463 PMID: 25232946
  38. Hansen, M.; Kilk, K.; Langel, Ü. Predicting cell-penetrating peptides. Adv. Drug Deliv. Rev., 2008, 60(4-5), 572-579. doi: 10.1016/j.addr.2007.09.003 PMID: 18045726

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