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Investigation of structures and properties of cyclic peptide nanotubes by experiment and molecular dynamics

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Abstract

In order to investigate the structures and properties of cyclic peptide nanotubes of cyclo[(-d-Phe-l-Ala) n = 3,4,5,6-], cyclo[(-d-Phe-l-Ala) n = 4-] was synthesized and self-assembled to nanotubes, and its structure and morphology of the nanotube were characterized by mass spectrometry (MS), fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). On the basis of these experimental results, the structures of cyclo[(-d-Phe-l-Ala) n = 3,4,5,6-] were characterized by molecular dynamics. In addition, the motion behaviors of H2O molecules in nanotubes were investigated by molecular dynamics using a COMPASS force field. Experimental results show that cyclo[(-d-Phe-l-Ala) n = 4-] peptides self-assemble into nanotube bundles. Molecular modeling results indicate that cyclic peptide nanotubes with n = 3, 4, 5 and 6 are very stable; these nanotubes have internal diameters of 5.9 Å, 8.1 Å, 10.8 Å and 13.1 Å and outer diameters of 18.2 Å, 21.7 Å, 23.4 Å and 25.9 Å respectively. Modeling results demonstrate that H2O molecules move in cooperation in single nanotube and they diffuse in one dimension, but they did not diffuse unilaterally due to the antiparallel ring stacking arrangement.

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References

  1. Hartgerink JD, Clark TD, Ghadiri MR (1998) Peptide nanotubes and beyond. Chem Eur J 4:1367–1372

    Article  CAS  Google Scholar 

  2. Brea RJ, Vazquez ME, Mosquera M, Castedo L, Granja JR (2007) Controlling multiple fluorescent signal output in cyclic peptide-based supramolecular systems. J Am Chem Soc 129:1653–1657

    Article  CAS  Google Scholar 

  3. Janshoff A, Dancil KPS, Steinem C, Greiner DP, Lin VSY, Gurtner C, Motesharei K, Sailor MJ, Ghadiri MR (1998) Macroporous p-type silicon Fabry-Perot layers. Fabrication, characterization, and applications in biosensing. J Am Chem Soc 120:12108–12116

    Article  CAS  Google Scholar 

  4. David G, Pierre BM (2001) Self-assembly of cyclic peptides into nanotubes and then into highly anisotropic crystalline materials. J Angew Chem Int Ed 40:4635–4638

    Article  Google Scholar 

  5. Ghadiri MR (1995) Self-assembled nanoscale tubular ensembles. Adv Mater 7:675–677

    Article  CAS  Google Scholar 

  6. De Santis P, Morosetti S, Rizzo R (1974) Conformational analysis of regular enantiomeric sequences. Macromolecules 7:52–58

    Article  Google Scholar 

  7. Ghadiri MR, Granja JR, Milligan RA, McRee DE, Khazanovich N (1993) Self-assembling organic nanotubes based on a cyclic peptide architecture. Nature 366:324–327

    Article  CAS  Google Scholar 

  8. Ghadiri MR, Granja JR, Buehler LK (1994) Artificial transmembrane ion channels from self-assembling peptide nanotubes. Nature 369:301–304

    Article  CAS  Google Scholar 

  9. Hartgerink JD, Granja JR, Milligan RA, Ghadiri MR (1996) Self-assembling peptide nanotubes. J Am Chem Soc 118:43–50

    Article  CAS  Google Scholar 

  10. Kim HS, Hartgerink JD, Ghadiri MR (1998) Oriented self-assembly of cyclic peptide nanotubes in lipid membranes. J Am Chem Soc 120:4417–4424

    Article  CAS  Google Scholar 

  11. Clark TD, Buriak JM, Kobayashi K, Isler MP, McRee DE, Ghadiri MR (1998) Cylindrical beta-sheet peptide assemblies. J Am Chem Soc 120:8949–8962

    Article  CAS  Google Scholar 

  12. Fernandez-Lopez S, Kim HS, Choi EC, Delgado M, Granja JR, Khasanov A, Kraehenbuehl K, Long G, Weinberger DA, Wilcoxen KM, Ghadiri MR (2001) Antibacterial agents based on the cyclic D, L-alpha-peptide architecture. Nature 412:452–455

    Article  CAS  Google Scholar 

  13. Amorin M, Castedo L, Granja JR (2003) New cyclic peptide assemblies with hydrophobic cavities, The structural and thermodynamic basis of a new class of peptide nanotubes. J Am Chem Soc 125:2844–2845

    Article  CAS  Google Scholar 

  14. Brea RJ, Lopez-Deber MP, Castedo L, Granja JR (2006) Synthesis of omega-(hetero)arylalkynylated alpha-amino acid by sonogashira-type reactions in aqueous media. J Org Chem 71:7870–7873

    Article  CAS  Google Scholar 

  15. Sanchez-Quesada J, Ghadiri MR, Bayley H, Braha O (2000) Cyclic peptides as molecular adapters for a pore-forming protein. J Am Chem Soc 122:11757–11766

    Article  CAS  Google Scholar 

  16. Clark TD, Buehler LK, Ghadiri MR (1998) Self-assembling cyclic beta(3)-peptide nanotubes as artificial transmembrane ion channels. J Am Chem Soc 120:651–656

    Article  CAS  Google Scholar 

  17. Horne WS, Ashkenasy N, Ghadiri MR (2005) Modulating charge transfer through cyclic D,L-alpha-peptide self-assembly. Chem Eur J 11:1137–1144

    Article  CAS  Google Scholar 

  18. Ortiz-Acevedo A, Xie H, Zorbas V, Sampson WM, Dalton AB, Baughman RH, Draper RK, Musselman IH, Dieckmann GR (2005) Diameter-selective solubilization of single-walled carbon nanotubes by reversible cyclic peptides. J Am Chem Soc 127:9512–9517

    Article  CAS  Google Scholar 

  19. Christoph AS (2004) Elements for the construction of molecular devices: template effects and self-assembly. J Phys Org Chem 17:967–972

    Article  CAS  Google Scholar 

  20. Ashkenasy G, Ghadiri MR (2004) Boolean logic functions of a synthetic peptide network. J Am Chem Soc 126:11140–11141

    Article  CAS  Google Scholar 

  21. Lewis JP, Pawley NH, Sankey OF (1997) Theoretical investigation of the cyclic peptide system cyclo[(D-Ala-Glu-D-Ala-Gln)(m=1-4)]. J Phys Chem B 101:10576–10583

    Article  CAS  Google Scholar 

  22. Jishi RA, Flores RM, Valderrama M, Lou L, Bragin J (1998) Equilibrium geometry and properties of cyclo[(Gly-D-Ala)4] and {cyclo[(Gly-D-Ala)4]}2 from density functional theory. J Phys Chem A 102:9858–9862

    Article  CAS  Google Scholar 

  23. Chen G, Su S, Liu R (2002) Theoretical studies of monomer and dimer of cyclo [(L-Phe1-D-Ala2)n] and cyclo[(-L-Phe1-D-MeN-Ala2 )n](n=3-6). J Phys Chem B 106:1570–1575

    Article  CAS  Google Scholar 

  24. Khurana E, Nielsen SO, Ensing B, Klein ML (2006) Self-assembling cyclic peptides, molecular dynamics studies of dimers in polar and nonpolar solvents. J Phys Chem B 110:18965–18972

    Article  CAS  Google Scholar 

  25. Hwang H, Schatz GC, Ratner MA (2006) Steered molecular dynamics studies of the potential of mean force of a Na+ or K+ ion in a cyclic peptide nanotube. J Phys Chem B 110:26448–26460

    Article  CAS  Google Scholar 

  26. Hwang H, Schatz GC, Ratner MA (2006) Ion current calculations based on three dimensional Poisson-Nernst-Planck theory for a cyclic peptide nanotube. J Phys Chem B 110:6999–7008

    Article  CAS  Google Scholar 

  27. Clark TD, Ghadiri MR (1995) Supramolecular design by covalent capture. design of a peptide cylinder via hydrogen-bond-promoted intermolecular olefin metathesis. J Am Chem Soc 117:12364–12365

    Article  CAS  Google Scholar 

  28. Rosenthal-Aizman K, Svensson G, Unden A (2004) Self-assembling peptide nanotubes from enantiomeric pairs of cyclic peptides with alternating D and L amino acid residues. J Am Chem Soc 126:3372–3373

    Article  CAS  Google Scholar 

  29. Dawson PE, Churchill MJ, Ghadiri MR, Kent SBH (1997) Modulation of reactivity in native chemical ligation through the use of thiol additives. J Am Chem Soc 119:4325–4329

    Article  CAS  Google Scholar 

  30. Ranganathan D (2001) Designer hybrid cyclopeptides for membrane ion transport and tubular structures. Acc Chem Res 34:919–930

    Article  CAS  Google Scholar 

  31. Bong DT, Ghadiri MR (2001) Self-assembling cyclic peptide cylinders as nuclei for crystal engineering. Angew Chem Int Edit 40:2163–2166

    Article  CAS  Google Scholar 

  32. Horne WS, Stout CD, Ghadiri MR (2003) A heterocyclic peptide nanotube. J Am Chem Soc 125:9372–9376

    Article  CAS  Google Scholar 

  33. Horne WS, Yadav MK, Stout CD, Ghadiri MR (2004) Heterocyclic peptide backbone modifications in an α-helical coiled coil. J Am Chem Soc 126:15366–15367

    Article  CAS  Google Scholar 

  34. Engels M, Bashford D, Ghadiri MR (1995) Structure and dynamics of self-assembling peptide nanotubes and the channel-mediated water organization and self-diffusion. a molecular dynamics study. J Am Chem Soc 117:9151–9158

    Article  CAS  Google Scholar 

  35. Tarek M, Maigret B, Chipot C (2003) Molecular dynamics investigation of an oriented cyclic peptide nanotube in DMPC bilayers. Biophys J 85:2287–2298

    Article  CAS  Google Scholar 

  36. Wang SS, Makofske R, Bach A (1980) Automated solid phase synthesis of thymosinal. Int J Pept Protein Res 15:1–4

    CAS  Google Scholar 

  37. Kobayashi K, Granja JR, Ghadiri MR (1995) Beta-sheet peptide architecture: measuring the relative stability of parallel vs. antiparallel beta-Sheets. Angew Chem Int Ed 34:95–98

    Article  CAS  Google Scholar 

  38. Ghadiri MR, Kobayashi K, Granja JR, Chadha RK, McRee DE (1995) The structural and thermodynamic basis for the formation of self-assembled peptide nanotubes. Angew Chem Int Ed 34:93–95

    Article  CAS  Google Scholar 

  39. Sun H (1995) Ab initio calculations and force field development for computer simulation of polysilanes. Macromolecules 28:701–712

    Article  CAS  Google Scholar 

  40. Sun H (1998) COMPASS: an ab initio force-field optimized for condensed-phase applications – overview with details on alkane and benzene compounds. J Phys Chem B 102:7338–7364

    Article  CAS  Google Scholar 

  41. Sun H, Ren P, Fried JR (1998) The COMPASS force field: parameterization and validation for polyphosphazenes. Comput Theor Polym Sci 8:229–246

    Article  CAS  Google Scholar 

  42. Krimm S, Bandekar J (1986) Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins. Adv Protein Chem 38:181–364

    Article  CAS  Google Scholar 

  43. Pavone V, Benedetti E, Blasio BD, Lombardi A, Pedone C, Tomasich L, Lorenzi GP (1989) Regularly alternating L, D-peptides. III. Hexacyclic peptides from valine or phenylalanine. Biopolymers 28:215–223

    Article  CAS  Google Scholar 

  44. Sun X, Lorenzi GP (1994) On the stacking of β-rings: the solution self-association behavior of two partially N-methylated cyclo(hexaleucines). Helv Chim Acta 77:1520–1526

    Article  CAS  Google Scholar 

  45. Bandekar J (1992) Amide modes and protein conformation. Biochim Biophys Acta 1120:123–143

    CAS  Google Scholar 

  46. Saviano M, Lombardi A, Pedone C, Blasio BD, Sun XC, Lorenzi GP (1994) A structural two-ring version of a tubular stack of β-rings in crystals of a cyclic D,L-hexapeptide. J Incl Phenom 18:27–36

    Article  CAS  Google Scholar 

  47. Granja JR, Ghadiri MR (1994) Channel-mediated transport of glucose across lipid bilayers. J Am Chem Soc 116:10785–10786

    Article  CAS  Google Scholar 

  48. Khazanovich N, Granja JR, McRee DE, Milligan RA, Ghadiri MR (1994) Nanoscale tubular ensembles with specified internal diameters. Design of a self-assembled nanotube with a 13 angstrom. pore. J Am Chem Soc 116:6011–6012

    Article  CAS  Google Scholar 

  49. Cheng HS, Cooper AC, Pez GP, Kostov MK, Piotrowski P, Stuart SJA (2005) Molecular dynamics simulations on the effects of diameter and chirality on hydrogen adsorption in single walled carbon nanotubes. J Phys Chem B 109:3780–3786

    Article  CAS  Google Scholar 

  50. Yang H, Liu Y, Zhang H, Li ZS (2006) Diffusion of single alkane molecule in carbon nanotube studied by molecular dynamics simulation. Polymer 47:7607–7610

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Materials Science and Engineering, Harbin Institute of Technology, Box 433, No. 92 West Dazhi Street, Harbin, 150001, P.R. China

    Jingchuan Zhu, Jie Cheng, Zhouxiong Liao & Zhonghong Lai

  2. School of Chemical and Environmental Engineering, Harbin University of Science and Technology, No. 52, Xuefu Road, Box 128, Harbin, 150040, P.R. China

    Bo Liu

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  1. Jingchuan Zhu
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Correspondence to Jie Cheng.

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Zhu, J., Cheng, J., Liao, Z. et al. Investigation of structures and properties of cyclic peptide nanotubes by experiment and molecular dynamics. J Comput Aided Mol Des 22, 773–781 (2008). https://doi.org/10.1007/s10822-008-9212-9

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