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Studies on the Conformations and Hydrogen-Bonding Interactions of RGD Tri-peptide in Aqueous Solutions by Molecular Dynamics Simulations and 2D-NOESY Spectroscopy

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Abstract

Molecular dynamic simulations and 1H-1H NOESY spectroscopy have been used to study the conformations and hydrogen bond interactions of RGD tri-peptide in aqueous solution. The properties are characterized by intramolecular distances, radius of gyration, root-mean-square deviation, and solvent-accessible surface. The RGD molecule is highly flexible in aqueous solutions and the conformations can shift between extended and folded states. Most of the time, RGD exists in the extended state in aqueous solution. The results in the MD simulations and 2D-NMR experiments are in good agreement.

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References

  1. Zhang, J.G., Krajden, O.B., Kainthan, R.K., Kizhakkedathu, J.N., Constantinescu, I., Brooks, D.E., Gyongyossy-Issa, M.I.C.: Conjugation to hyperbranched polyglycerols improves RGD-mediated inhibition of platelet function in vitro. Bioconjug. Chem. 19, 1241–1247 (2008)

    Article  CAS  Google Scholar 

  2. Castelletto, V., Stain, C., Connon, S.: Slow-release RGD-peptide hydrogel monoliths. Langmuir 28, 12575–12580 (2012)

    Article  CAS  Google Scholar 

  3. Seo, J., Kakinoki, S., Inoue, Y., Yamaoka, T., Ishihara, K., Yui, N.: Inducing rapid cellular response on RGD-binding threaded macromolecular surfaces. J. Am. Chem. Soc. 135, 5513–5516 (2013)

    Article  CAS  Google Scholar 

  4. Amin, M., Badiee, A., Jaafari, M.R.: Improvement of pharmacokinetic and antitumor activity of PEGylated liposomal doxorubicin by targeting with N-methylated cyclic RGD peptide in mice bearing C-26 colon carcinomas. Int. J. Pharm. 458, 324–333 (2013)

    Article  CAS  Google Scholar 

  5. Gupta, A.S., Huang, G., Lestini, B.J., Sagnella, S., Kottke-Marchant, K., Marchant, R.E.: RGD-modified liposomes targeted to activated platelets as a potential vascular drug delivery system. Thromb. Haemost. 93, 106–114 (2005)

    Google Scholar 

  6. Chakraborty, S., Shi, J., Kim, Y., Zhou, Y., Jia, B., Wang, F., Liu, S.: Evaluation of 111In-labeled cyclic RGD peptides: tetrameric not tetravalent. Bioconjug. Chem. 21, 969–978 (2010)

    Article  CAS  Google Scholar 

  7. Deng, D., Qu, L., Zhang, J., Ma, Y., Gu, Y.: Quaternary Zn–Ag–In–Se quantum dots for biomedical optical imaging of RGD-modified micelles. ACS Appl. Mater. Interfaces 5, 10858–10865 (2013)

    Article  CAS  Google Scholar 

  8. Yin, R., Zheng, H., Xi, T., Xu, H.: Effect of RGD-4C position is more important than disulfide bonds on antiangiogenic activity of RGD-4C modified endostatin derived synthetic polypeptide. Bioconjug. Chem. 21, 1142–1147 (2010)

    Article  CAS  Google Scholar 

  9. Zhen, Z., Tang, W., Chen, H., Lin, X., Todd, T., Wang, G., Cowger, T., Chen, X., Xie, J.: RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors. ACS Nano 7, 4830–4837 (2013)

    Article  CAS  Google Scholar 

  10. Muir, J.M.R., Costa, D., Idriss, H.: DFT computational study of the RGD peptide interaction with the rutile TiO2 (110) surface. Surf. Sci. 624, 8–14 (2014)

    Article  CAS  Google Scholar 

  11. Sheu, J.R., Huang, T.F.: Ex-vivo and in vivo antithrombotic effect of triflavin, an RGD-containing peptide. Pharm. Pharmacol. 46, 58–62 (1994)

    Article  CAS  Google Scholar 

  12. Zhou, Y., Kim, Y., Lu, X., Liu, S.: Evaluation of 99mTc-labeled cyclic RGD dimers: impact of cyclic RGD peptides and 99mTc chelates on biological properties. Bioconjug. Chem. 23, 586–595 (2012)

    Article  CAS  Google Scholar 

  13. Mokhtarieh, A.A., Kim, S., Lee, Y., Chung, B., Lee, M.K.: Novel cell penetrating peptides with multiple motifs composed of RGD and its analogs. Biochem. Biophys. Res. Commun. 432, 359–364 (2013)

    Article  CAS  Google Scholar 

  14. Cai, W., Chen, X.: Multimodality molecular imaging of tumor angiogenesis. J. Nucl. Med. 49, 113S–128S (2008)

    Article  CAS  Google Scholar 

  15. Li, Z.B., Chen, K., Chen, X.: 68Ga-labeled multimeric RGD peptides for micro PET imaging of integrin αVβ3 expression. Eur. J. Nucl. Med. Mol. Imaging 35, 1100–1108 (2008)

    Article  CAS  Google Scholar 

  16. Yu, Y., Wang, Q., Liu, Y., Xie, Y.: Molecular basis for the targeted binding of RGD-containing peptide to integrin αVβ3. Biomaterials 35, 1667–1675 (2014)

    Article  CAS  Google Scholar 

  17. Wu, C., Chen, M., Guo, C., Zhao, X., Yuan, C.: Peptide-TiO2 interaction in aqueous solution: conformational dynamics of RGD using different water models. J. Phys. Chem. B 114, 4692–4701 (2010)

    Article  CAS  Google Scholar 

  18. Feng, X., Cheng, Y., Wu, Q., Zhang, J., Xu, T.: NMR-NOE and MD simulation study on phospholipid membranes: dependence on membrane diameter and multiple time scale dynamics. J. Phys. Chem. B 115, 9106–9115 (2011)

    Article  Google Scholar 

  19. Pozzo, A.D., Ni, M., Muzi, L., Castiglione, R., Mondelli, R., Mazzini, S., Penco, S., Pisano, C., Castorina, M., Giannini, G.: Incorporation of the unusual Cα-fluoroalkylamino acids into cyclopeptides: synthesis of arginine–glycine–aspartate (RGD) analogues and study of their conformational and biological behavior. J. Med. Chem. 49, 1808–1817 (2006)

    Article  Google Scholar 

  20. Denkova, P.S., Lokeren, L., Verbruggen, I., Willem, R.: Self-aggregation and supramolecular structure investigations of triton X-100 and SDP2S by NOESY and diffusion ordered NMR spectroscopy. J. Phys. Chem. B 112, 10935–10941 (2008)

    Article  CAS  Google Scholar 

  21. Zhang, R., Wu, W.: Studies on the structures and interactions of glutathione in aqueous solution by molecular dynamics simulations and nmr spectroscopy. J. Mol. Liq. 162, 20–25 (2011)

    Article  CAS  Google Scholar 

  22. Zhang, R., Huang, J.M., Meng, X., Wu, W.J.: Molecular dynamics simulations and NMR experimental study of oxidized glutathione in aqueous solution. J. Solution Chem. 41, 879–887 (2012)

    Article  CAS  Google Scholar 

  23. Zhang, R., Zheng, D., Pan, Y., Luo, S., Wu, W., Li, H.: All-atom simulation and excess properties study on intermolecular interactions of amide–water system. J. Mol. Struct. 875, 96–100 (2008)

    Article  CAS  Google Scholar 

  24. Jorgensen, W.L., Maxwell, D.S., Tirado-Rives, J.: Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 118, 11225–11236 (1996)

    Article  CAS  Google Scholar 

  25. Jorgensen, W.L., Swenson, C.J.: Optimized intermolecular potential functions for amides and peptides. structure and properties of liquid amides. J. Am. Chem. Soc. 107, 569–578 (1985)

    Article  CAS  Google Scholar 

  26. Mark, P., Nilsson, L.: Structure and dynamics of the TIP3P, SPC, and SPC/E water models at 298 K. J. Phys. Chem. A 105, 9954–9960 (2001)

    Article  CAS  Google Scholar 

  27. Berweger, C.D., Gunsteren, W.F., Müller-Plathe, F.: Force field parametrization by weak coupling te-engineering SPC water. Chem. Phys. Lett. 232, 429–436 (1995)

    Article  CAS  Google Scholar 

  28. Dudek, M.J., Ramnarayan, K., Ponder, J.W.: Protein structure prediction using a combination of sequence homology and global energy minimization: II. Energy functions. J. Comput. Chem. 19, 548–573 (1998). http://dasher.wustl.edu/tinker. Accessed 28 Mar 2014

  29. Lei, Y., Li, H., Pan, H., Han, S.: Structures and hydrogen bonding analysis of N,N-dimethylformamide and N,N-dimethylformamide–water mixtures by molecular dynamics simulations. J. Phys. Chem. A 107, 1574–1583 (2003)

    Article  CAS  Google Scholar 

  30. Connolly, M.L.: Analytical molecular surface calculation. J. Appl. Crystallogr. 16, 548–558 (1983)

    Article  CAS  Google Scholar 

  31. Zheng, G., Stait-Gardner, T., Anil Kumar, P.G., Torres, A.M., Price, W.S.: PGSTE-WATERGATE: an STE-based PGSE NMR sequence with excellent solvent suppression. J. Magn. Reson. 191, 159–163 (2008)

    Article  CAS  Google Scholar 

  32. Clairac, R.P.L., Geierstanger, B.H., Mrksich, M., Dervan, P.B., Wemmer, D.E.: NMR characterization of hairpin polyamide complexes with the minor groove of DNA. J. Am. Chem. Soc. 119, 7909–7916 (1997)

    Article  Google Scholar 

  33. Lei, Y., Li, H., Zhang, R., Han, S.: Molecular dynamics simulations of biotin in aqueous solution. J. Phys. Chem. B 108, 10131–10137 (2004)

    Article  CAS  Google Scholar 

  34. Lo, J., Yen, H., Tsai, C., Chen, B., Hou, S.: Interaction between hydrophobically modified 2-hydroxyethyl cellulose and sodium dodecyl sulfate studied by viscometry and two-dimensional NOE NMR spectroscopy. J. Phys. Chem. B 118, 6922–6930 (2014)

    Article  CAS  Google Scholar 

  35. Schedlbauer, A., Coudevylle, N., Auer, R., Kloiber, K., Tollinger, M., Konrat, R.: Autocorrelation analysis of NOESY data provides residue compactness for folded and unfolded proteins. J. Am. Chem. Soc. 131, 6038–6039 (2009)

    Article  CAS  Google Scholar 

  36. Khodov, I.A., Nikiforov, M.Y., Alper, G.A., Blokhin, D.S., Efimov, S.V., Klochkov, V.V., Georgi, N.: Spatial structure of felodipine dissolved in DMSO by 1D NOE and 2D NOESY NMR spectroscopy. J. Mol. Struct. 1035, 358–362 (2013)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No: 20903026), the Talents Introduction Foundation for Universities of Guangdong Province (2011) and the Science and Technology Planning Project of Guangzhou (No. 2013J4100071).

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Authors and Affiliations

  1. Laboratory of Physical Chemistry, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China

    Rong Zhang, GuoDong Huang, Lin Chen & Wenjuan Wu

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  1. Rong Zhang
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Correspondence to Rong Zhang.

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Zhang, R., Huang, G., Chen, L. et al. Studies on the Conformations and Hydrogen-Bonding Interactions of RGD Tri-peptide in Aqueous Solutions by Molecular Dynamics Simulations and 2D-NOESY Spectroscopy. J Solution Chem 44, 1281–1291 (2015). https://doi.org/10.1007/s10953-015-0333-1

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