Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 30174
Molecular Dynamics and Circular Dichroism Studies on Aurein 1.2 and Retro Analog

Authors: Safyeh Soufian, Hoosein Naderi-Manesh, Abdoali Alizadeh, Mohammad Nabi Sarbolouki


Aurein 1.2 is a 13-residue amphipathic peptide with antibacterial and anticancer activity. Aurein1.2 and its retro analog were synthesized to study the activity of the peptides in relation to their structure. The antibacterial test result showed the retro-analog is inactive. The secondary structural analysis by CD spectra indicated that both of the peptides at TFE/Water adopt alpha-helical conformation. MD simulation was performed on aurein 1.2 and retro-analog in water and TFE in order to analyse the factors that are involved in the activity difference between retro and the native peptide. The simulation results are discussed and validated in the light of experimental data from the CD experiment. Both of the peptides showed a relatively similar pattern for their hydrophobicity, hydrophilicity, solvent accessible surfaces, and solvent accessible hydrophobic surfaces. However, they showed different in directions of dipole moment of peptides. Also, Our results further indicate that the reversion of the amino acid sequence affects flexibility .The data also showed that factors causing structural rigidity may decrease the activity. Consequently, our finding suggests that in the case of sequence-reversed peptide strategy, one has to pay attention to the role of amino acid sequence order in making flexibility and role of dipole moment direction in peptide activity. KeywordsAntimicrobial peptides, retro, molecular dynamic, circular dichroism.

Keywords: Antimicrobial peptides, retro, molecular dynamic, circular dichroism.

Digital Object Identifier (DOI):

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 1472


[1] Leban, J. J., Kull, F. C., Jr., Landavazo, A., Stockstill, B., and McDermed, J. D. Development of Potent Gastrin-Releasing Peptide Antagonists Having a D-Pro- (CH2NH)-Phe-NH2 C Terminus. Proc. Natl. Acad. Sci 90: 1922-1926. 1993.
[2] Chorev, M. The partial retro-inverso modification: A road traveled together. Biopolymers 80 (2-3): 67-84 .2005.
[3] Peer R. E. Mittl, C. D., David Sargent, Niankun Liu, Stephan Klauser, Richard M. Thomas. The retro-GCN4 leucine zipper sequence forms a stable three-dimensional structure. PNAS 97: 2562-2566. 2000
[4] Stephan Lorenzen, C. G., Robert Preissner and Cornelius Frömmel. Inverse sequence similarity of proteins does not imply structural similarity. FEBS Letters 545: 105-109. 2003.
[5] Fischer, P. The design,synthesis and application of stereochemical and directional peptide isomers: A critical review. Current Protein & Peptide Science 4 (5): 339-356. 2003
[6] Guptasarma. FEBS Lett, Reversal of peptide backbone direction may result in the mirroring of protein structure , 310: 205-210. 1992.
[7] Zhao M, K. m. H., Mokotoff M. Briand retro-inverso peptide corresponding to the GH loop of foot-and-mouth disease virus elicits high levels of long-lasting protective neutralizing antibodies. Proc Natl Acad Sci U S 94(23): 12545-12550. 1997
[8] Meziere C, V. M., Dumortier H, Lo-Man R, Leclerc C, Guillet JG, Briand JP, Muller S. In vivo T helper cell response to retro-inverso peptidomimetics. J Immunol 159(7): 3230-3237. 1997.
[9] Carmona AK, J. L. Inhibition of angiotensin converting enzyme and potentiation of bradykinin by retro-inverso analogues of short peptides and sequences related to angiotensin I and bradykininl. Biochem Pharmaco 51(8): 1051-1060. 1996.
[10] Bonelli F, P. A., Verdini AS. . Solid phase synthesis of retro-inverso peptide analogues. Synthesis and biological activity of the partially modified retro-inverso analogue of the bradykinin potentiating peptide BPP9a (gLys6, (RS)-mPhe7, Ala8] .Int J Pept Protein Res 24(6): 553- 556. 1984.
[11] Rozek, T., J. H. Bowie, J. C. Wallace, M. J. Tyler. The antibiotic and anticancer active aurein peptides from the Australian Bell Frogs Litoria aurea and Litoria raniformis. Part 2. Sequence determination using electrospray mass spectrometry. Rapid Commun. Mass Spectrom 14: 2002-2011. 2000.
[12] Rozek T., K. L. W., J. H. Bowie, I. N. Olver, J. A. Carver, J. C. Wallace, and M. J. Tyler. The antibiotic and anticancer active aurein peptides from the Australian Bell Frogs Litoria aurea and Litoria raniformis the solution structure of aurein 1.2. Eur. J. Biochem 267: 5330-5341. 2000.
[13] Dennison, S. R. W., Michelle; Harris, Frederick; Phoenix, David Anticancer ╬▒-Helical Peptides and Structure / Function Relationships Underpinning Their Interactions with Tumour Cell Membranes. Current Protein and Peptide Science 7: 487-499. 2006.
[14] Sarah R. Dennison a, F. H. b., David A. Phoenix. The interactions of aurein 1.2 with cancer cell membranes. Biophysical Chemistry 127: 78- 83. 2007.
[15] Fields, G. B., Z. Tian, and G. Barany. Synthetic peptide: a user-s guide. 77-183. 1992
[16] Furka, A., F. Sebestyen, M. Asgedom, and G. Dibo. General method for rapid synthesis of multicomponent peptide mixtures. Int. J. Peptide Protein Res 37: 487-493. 1991
[17] Goodman, M. Synthesis of Peptides and Peptidomimetics, Thieme/Houben-Weyl Series.2005.
[18] ChemPep Protocol, Phase-Peptide-Synthesis.htm, 2006
[19] A.J. Smith, B. J. S. AAA, Postcolumn amino acid analysis. Methods in Molecular Biology: Protein Sequencing Protocols 64,: 139-146. 1997.
[20] Vydac, G. The Handbook of analysis and purification of peptide and proteins by reversed -phase HPLC.2002.
[21] Igor A. Kaltashov, S. J. E (Ed.) Conformation and Dynamics of Biomolecules.2005.
[22] Hancock, b. in first Gordon conference on antimicrobial peptides.
[23] Hancock, R. Peptide antibiotics. Lancet 349: 418 - 422. 1997.
[24] Woody, R. Circular dichroism and conformation of unordered polypeptides. Adv biophys Chem 2: 37-79. 1992.
[25] W.J. Waddell. A simple ultraviolet spectrophotometric method for the determination of protein. J. Lab. Clin. Med 48: 311-314. 1956.
[26] HyperChem® Release 7 for Windows, Hypercube. 2002.
[27] Berendsen H. J. C., P., J. P. M., van Gunsteren, W. F., Di Nola, A. & Haak, J. R. Molecular Dynamics with Coupling to an External Bath. J. Chem. Phys 81: 3684-3690. 1984.
[28] van Gunsteren W. F., D., X. & Mark, A. E. GROMOS forcefield. In Encyclopedia of Computational Chemistry. Encycl. Comput. Chem 2: 1211-1216. 1998.
[29] van Gunsteren WF, B. S., Eising AA, H├╝nenberger PH,Kr├╝ger P, Mark AE, Scott WRP and Tironi IG. Biomolecular simulation: the GROMOS96 manual and user guide. 1996
[30] Hess, B., Bekker, H., Berendsen, H.J.C., and Fraaije, J.G.E.M. LINCS: A linear constraint solver for molecular simulations. J. Comp. Chem. 18: 1463-1472. 1997.
[31] Deserno, M. a. H., C. 1998. . How to mesh up Ewald sums:A theoretical and numerical comparison of various particle mesh routines. J. Chem. Phys 109: 7678-7693. 1998.
[32] Gromacs User Manual.2006.
[33] Kabsch, W. and C. Sander. Dictionary of protein secondary structure: pattern-recognition of hydrogen-bonded and geometrical features. Biopolymers 22: 2577-2637. 1983.
[34] Taylor, W. R. Identification of protein sequence homology by consensus template alignment. J. Mol. Bio 188: 233-258. 1986.
[35] Johannes Buchner, T. K. Protein Folding Handbook, Vol. 1. 2005.
[36] S Gnanakaran, H. N., John Portman. Peptide folding simulations. Current Opnion in structural Biology 13: 168-174. 2003.
[37] Doig, A. J. a. B., R.L. N- and C-capping preferences for all 20 amino acids in -helical peptides. Protein Sci. 4: 1325-1336. 1995.
[38] Ernesto E. Ambroggio, F. S., John H. Bowie, Gerardo D. Fidelio, Luis A. Bagatolli. Direct visualization of membrane leakage induced by the antibiotic peptides: Maculatin, Citropin and Aurein. Biophys J. 89: 1874-1881. 2005.
[39] H.A.Carlson. Protein flexibility is an important component of structurebased drug discovery. Curr. Pharm. Des 8: 1571-1578. 2002.
[40] R. Antoine, I. C., D. Rayane, M. Broyer, Ph. Dugourd, G. Breaux, F.C. Hagemeister, D. Pippen, R.R. Hudgins and M.F. Jarrold,. Electric dipole moments and conformations of isolated peptides. Eur. Phy. J. 20: 583. 2002.
[41] Simonson. Dielectric relaxation in proteins: macroscopic and microscopic models. Int J Quantum Chem 73: 45-57. 1999.
[42] Persson, S., Killian, A., and Lindblom, G. Molecular ordering, and 2HNMR, Biophys. J. 75: 1365-1371. 1998.