Inter- versus intra-molecular cyclization of tripeptides containing tetrahydrofuran amino acids: a density functional theory study on kinetic control

Abstract

Density functional B3LYP method was used to investigate the preference of intra- and inter-molecular cyclizations of linear tripeptides containing tetrahydrofuran amino acids. Two distinct model pathways were conceived for the cyclization reaction, and all possible transition states and intermediates were located. Analysis of the energetics indicate intermolecular cyclization being favored by both thermodynamic and kinetic control. Geometric and NBO analyses were performed to explain the trends obtained along both the reaction pathways. Conceptual density functional theory-based reactive indices also show that reaction pathways leading to intermolecular cyclization of the tripeptides are relatively more facile compared to intramolecular cyclization.

DFT- and NBO-based analysis of intra- and inter-molecular cyclizations of linear tripeptides containing tetrahydrofuran amino acids show the intermolecular path as favored by both thermodynamic and kinetic control

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

References

  1. 1.

    Gao X, Matsui H (2005) Peptide-based nanotubes and their applications in bionanotechnology. Adv Mater 17:20372050

    Google Scholar 

  2. 2.

    Ulijn RV, Smith AM (2008) Designing peptide based nanomaterials. Chem Soc Rev 37:664675

    Article  Google Scholar 

  3. 3.

    Wipf P, Uto Y (2000) Total synthesis and revision of stereochemistry of the marine metabolite trunkamide A. J Org Chem 65:1037

    Article  CAS  Google Scholar 

  4. 4.

    Faulkner DJ (1999) Marine natural products. Nat Prod Rep 16:155

    Article  Google Scholar 

  5. 5.

    Wipf P (1998) In alkaloids: chemical and biological perspectives. Pelletier SW (ed) Pergamon, New York 187

  6. 6.

    Wipf P (1995) Synthetic studies of biologically active marine cyclopeptides. Chem Rev 95:2115

    Article  CAS  Google Scholar 

  7. 7.

    Pettit GR (1994) Marine animal and terrestrial plant anticancer constituents. Pure Appl Chem 66:2271

    Article  CAS  Google Scholar 

  8. 8.

    Davidson BS (1993) Ascidians: producers of amino acid-derived metabolites. Chem Rev 93:1771

    Article  CAS  Google Scholar 

  9. 9.

    Haberhauer G, Rominger F (2002) Synthesis of a new class of imidazole-based cyclic peptides. Tetrahedron Lett 43:6335

    Article  CAS  Google Scholar 

  10. 10.

    Roy RS, Gehring AM, Milne JC, Belshaw PJ, Walsh CT (1999) Thiazole and oxazole peptides: biosynthesis and molecular machinery. Nat Prod Rep 16:249

    Article  CAS  Google Scholar 

  11. 11.

    Wipf P, Fritch PC, Gieb SJ, Sefler AM (1998) Conformational studies and structure-activity analysis of Lissoclinamide 7 and related cyclopeptide alkaloids. J Am Chem Soc 120:4105

    Article  CAS  Google Scholar 

  12. 12.

    Li Y-M, Miline JC, Madison LL, Kollerand R, Walsh CT (1996) From peptide precursors to oxazole and thiazole containing peptide antibiotics: microcin B17 synthase. Science 274:1188

    Article  CAS  Google Scholar 

  13. 13.

    Foster MP, Concepcion GP, Caraan GB, Ireland CM (1992) Bistratamides C and D. Two new oxazole-containing cyclic hexapeptides isolated from a philippine lissoclinum bistratum ascidian. J Org Chem 57:6671

    Article  CAS  Google Scholar 

  14. 14.

    Graf von Roedern E, Kessler H (1994) A sugar amino acid as a novel peptidomimetic. Angew Chem Int Ed Engl 33:687–689

    Article  Google Scholar 

  15. 15.

    Gruner SAW, Locardi E, Lohof E, Kessler H (2002) Carbohydrate based mimetics in drug design: sugar amino acids and carbohydrate scaffolds. Chem Rev 102:491–514

    Article  CAS  Google Scholar 

  16. 16.

    Levine DP (2006) Vancomycin: a history. Clin Infect Dis 42:S5S12

    Article  Google Scholar 

  17. 17.

    Rüegger A, Kuhn M, Lichti H, Loosli H-R, Huguenin R, Quiquerez C, von Wartburg A (1976) Cyclosporin A, a peptide metabolite from trichoderma polysporum (Link ex Pers.) Rifai, with a remarkable immunosuppressive activity. Helv Chim Acta 59:10751092

    Article  Google Scholar 

  18. 18.

    Gause GF, Brazhnikova MG (1944) Gramicidin S and its use in the treatment of infected wounds. Nature 154:703

    Article  Google Scholar 

  19. 19.

    Jiang S, Li Z, Ding K, Roller P (2008) Recent progress of synthetic studies to peptide and peptidomimetic cyclization. Curr Org Chem 12:15021542

    Article  Google Scholar 

  20. 20.

    Haubner R, Gratias R, Diefenbach B, Goodman SL, Jonczyk A, Kessler H (1996) Structural and functional aspects of RGD containing cyclic pentapeptides as highly potent and selective integrin α v β 3 antagonists. J Am Chem Soc 118:74617472

    Google Scholar 

  21. 21.

    Walensky LD, Kung AL, Escher I, Malia TJ, Barbuto S, Wright R, Wagner G, Verdine GL, Korsmeyer SJ (2004) Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305:14661470

    Article  Google Scholar 

  22. 22.

    Seebach D, Gardiner J (2008) β -Peptidic peptidomimetics. Acc Chem Res 41:13661375

    Article  Google Scholar 

  23. 23.

    Seebach D, Beck AK, Bierbaum D (2004) The world of beta- and gamma-peptides comprised of homologated proteinogenic amino acids and other components. J Chem Biodivers 1:1111–1239

    Article  CAS  Google Scholar 

  24. 24.

    Chakraborty TK, Srinivasu P, Tapadar S, Mohan BK (2005) Sugar amino acids in designing new molecules. Glycoconjugate J 22:83–93

    Article  CAS  Google Scholar 

  25. 25.

    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 

  26. 26.

    van Maarseveen JH, Horne WS, Ghadiri MR (2005) Efficient route to C2 symmetric heterocyclic backbone modified cyclic peptides. Org Lett 7:4503–4506

    Article  Google Scholar 

  27. 27.

    Ghorai A, Gayen A, Kulsi G, Padmanaban E, Laskar A, Achari B, Mukhopadhyay C, Chattopadhyay P (2011) Simultaneous parallel and antiparallel self-assembly in a triazole/amide macro cycle conformationally homologous to d-, l–amino acid based cyclic peptides: NMR and molecular modeling study. Org Lett 13:5512–5515. doi:10.1021/ol2022356

    Google Scholar 

  28. 28.

    Driggers EM, Hale SP, Lee J, Terrett NK (2008) Macrocycles for drug discovery an underexploited structural class. Nat Rev Drug Disc 7:608–624

    Article  CAS  Google Scholar 

  29. 29.

    White CJ, Yudin AK (2011) Contemporary strategies for peptide macrocyclization. Nat Chem 3:509–524

    Article  CAS  Google Scholar 

  30. 30.

    Jelokhani-Niaraki M, Kondejewski LH, Wheaton LC, Hodges RS (2009) Effect of ring size on conformation and biological activity of cyclic cationic antimicrobial peptides. J Med Chem 52:2090–2097

    Article  CAS  Google Scholar 

  31. 31.

    Bertram M, Hannam JS, Jolliffe KA, Gonzalez-Lopez de Turiso F, Pattenden G (1999) The synthesis of novel thiazole containing cyclic peptides via cyclooligomerization reactions. Synlett 1723–1726

  32. 32.

    Baldauf C, Günther R, Hofmann H-J (2004) δ -Peptides and δ amino acids as tools for peptide structure design-A theoretical study. J Org Chem 69:6214

    Article  CAS  Google Scholar 

  33. 33.

    Baldauf C, Günther R, Hofmann H-J (2006) Helix formation in α,γ-and β ,γ-hybrid peptides: Theoretical insights into mimicry of α-andβ-peptides. J Org Chem 71:1200–1208

    Article  CAS  Google Scholar 

  34. 34.

    Martinek TA, Mándity IM, Fūlōp L, Tóth GK, Vass E, Hollósi M, Forró E, Fūlōp F (2006) Effects of the alternating backbone configuration on the secondary structure and self-assembly of β -peptides. J Am Chem Soc 128:13539–13544

    Article  CAS  Google Scholar 

  35. 35.

    Jockusch RA, Talbot FO, Rogers PS, Simone MI, Fleet GWJ, Simons JP (2006) Carbohydrate amino acids: the intrisic conformational preference for a β -turn-type structure in a carbopeptoid building block. J Am Chem Soc 128:16771–16777

    Article  CAS  Google Scholar 

  36. 36.

    Sandvoss LM, Carlson HA (2003) Conformational behavior fo β proline oligomers. J Am Chem Soc 125:15855–15862 C

    Article  CAS  Google Scholar 

  37. 37.

    Zhong H, Carlson HA (2006) Conformational studies of polyprolines. J Chem Theory Comput 2:342–353

    Article  CAS  Google Scholar 

  38. 38.

    D’hooghe M, Catak S, Stankovič S, Waroquier M, Kim Y, Ha HJ, Speybroeck VV, Kimpe ND (2010) Systematic study of Halide induced ring opening of 2-substituted aziridinium and theoretical rationalization of the reaction pathways. Eur J Org Chem 4920–4931

  39. 39.

    Chakraborty TK, Tapadar S, Kumar SK (2002) Cyclic trimer of 5-(aminomethyl)-2-furancarboxylic acid as a novel synthetic receptor for Carboxylate recognition. Tetrahedron Lett 43:1317–1320

    Article  CAS  Google Scholar 

  40. 40.

    Chakraborty TK, Srinivasu P, Bikshapathy E, Nagaraj R, Vairamani M, Kumar SK, Kunwar AC (2003) Cyclic homooligomers of furanoid sugar amino acids. J Org Chem 68:6257–6263

    Article  CAS  Google Scholar 

  41. 41.

    Chakraborty TK, Koley D, Rapolu R, Krishnakumari V, Nagaraj R, Kunwar AC (2008) Synthesis, conformational analysis and biological studies of cyclic cationic antimicrobial peptides containing sugar amino acids. J Org Chem 73:8731–8744

    Article  CAS  Google Scholar 

  42. 42.

    Pal S, Mitra K, Azmi S, Ghosh JK, Chakraborty TK (2011) Towards the synthesis of sugar amino acid containing antimicrobial noncytotoxic CAP conjugates with gold nanoparticles and their mechanistic study towards cell disruption. Org Biomol Chem 9:4806–4810

    Article  CAS  Google Scholar 

  43. 43.

    Leonard MS, Joullie MM (2002) Encyclopedia of reagents for organic synthesis. Wiley, New York

    Google Scholar 

  44. 44.

    Kohn W, Becke AD, Parr RG (1996) Density functional theory of electronic structure. J Phys Chem 100:12974–12980

    Article  CAS  Google Scholar 

  45. 45.

    Kumar NVS, Sharma P, Singh H, Koley D, Roy S, Chakraborty TK (2010) Preferential mode of cyclization of tetrahydrofuran amino acids containing peptides: some theoretical insights. J Phys Org Chem 23:238–245

    CAS  Google Scholar 

  46. 46.

    Chakraborty TK, Roy S, Koley D, Dutta SK, Kunwar AC (2006) Conformational analysis of some C2-Symmetric cyclic peptides containing tetrahydrofuran amino acids. J Org Chem 71:6240–6243

    Article  CAS  Google Scholar 

  47. 47.

    Joullié MM, Lassen KM (2010) Evolution of amide bond formation. ARKIVOC viii:189–250

    Google Scholar 

  48. 48.

    Oie T, Loew GH, Burt SK, Binkley JS, MacElroy RD (1982) Quantum chemical studies of a model for peptide bond formation: formation of formamide and water from ammonia and formic acid. J Am Chem Soc 104:6169–6174

    Article  CAS  Google Scholar 

  49. 49.

    Jensen JH, Baldridge KK, Gordon MS (1992) Uncatalyzed peptide bond formation in the gas phase. J Phys Chem 96:8340

    Article  CAS  Google Scholar 

  50. 50.

    Krug JP, Popelier PLA, Bader RFW (1992) Theoretical study of neutral and of acid and base-promoted hydrolysis of formamide. J Phys Chem 96:7604–7616

    Article  CAS  Google Scholar 

  51. 51.

    Antonczak S, Ruiz-López MF, Rivail JL (1994) Ab initio analysis of water-assisted reaction mechanisms in amide hydrolysis. J Am Chem Soc 116:3912–3921

    Article  CAS  Google Scholar 

  52. 52.

    Pan B, Ricci MS, Trout BL (2011) A molecular mechanism of hydrolysis of peptide bonds at neutral pH using a model compound. J Phys Chem B 115:5958–5970

    Article  CAS  Google Scholar 

  53. 53.

    Sybyl version7.2, c.o.http://www.tripos.com

  54. 54.

    Gaurrand S, Desjardins S, Meyer C, Bonnet P, Argoullon JM, Oulyadi H, Guillemont J (2006) Conformational analysis of r207910, a new drug candidate for the treatment of tuberculosis, by a combined NMR and molecular modeling approach. Chem Biol Drug Des 68:77–84

    Article  CAS  Google Scholar 

  55. 55.

    Becke AD (1988) Density-functional exchange energy approximation with correct asymptotic behavior. Phys Rev A 38:3098–3100

    Article  CAS  Google Scholar 

  56. 56.

    Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789

    Article  CAS  Google Scholar 

  57. 57.

    Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652

    Article  CAS  Google Scholar 

  58. 58.

    Hehre WJ, Radom L, Schleyer PVR, Pople JA (1986) Ab initio molecular orbital theory. Wiley-Interscience, New York

    Google Scholar 

  59. 59.

    Guimarães CRW, Repasky MP, Chandrasekhar J, Tirado-Rives J, Jorgensen WL (2003) Contributions of conformational compression and preferential transition state stabilization to the rate enhancement by chorismate mutase. J Am Chem Soc 125:6892–6899

    Article  Google Scholar 

  60. 60.

    Zhang X, Bruice TC (2007) Diels-alder ribozyme catalysis: a computational approach. J Am Chem Soc 129:1001–1007

    Article  CAS  Google Scholar 

  61. 61.

    Gorb L, Asensio A, Tuñón I, Ruiz-López MF (2005) The mechanism of formamide hydrolysis in water from ab initio claculations and simulations. Chem Eur J 11:6743–6753

    Article  CAS  Google Scholar 

  62. 62.

    Frisch MJ et al (2003) Gaussian03, revision B.05; Gaussian, Pittsburg, PA

  63. 63.

    Laidler KJ (1987) Chemical kinetics, 3rd edn. Harper & Row, New York

    Google Scholar 

  64. 64.

    Chiodo SG, Leopoldini M, Russo N, Toscano M (2010) The inactivation of lipid peroxide radical by quercetin A. Theor Insight 12:7662–7670

    CAS  Google Scholar 

  65. 65.

    Černý J, Hobza P (2007) Non-covalent interactions in biomacro molecules. Phys Chem Chem Phys 9:5291–5302

    Google Scholar 

  66. 66.

    Chalupský J, Vondrášek J, Špirko V (2008) Quasiplanarity of the peptide bond. J Phys Chem A 112:693–699

    Article  Google Scholar 

  67. 67.

    Bednárová L, Maloň P, Bouř P (2007) Spectroscopic properties of the nonplanar amide group: a computational study. Chirality 19:775–786

    Article  Google Scholar 

  68. 68.

    Rick SW, Cachau RE (2000) The nonplanarity of the peptide group: molecular dynamics simulations with a polarizable two-state model for the peptide bond. J Chem Phys 112:5230

    Article  CAS  Google Scholar 

  69. 69.

    Ramek M, Yu C-H, Sakon J, Schäfer L (2000) Ab initio study of the conformational dependence of the nonplanarity of the peptide group. J Phys Chem A 104:9636–9645

    Article  CAS  Google Scholar 

  70. 70.

    MacArthur MW, Thornton JM (1996) Deviations from planarity of the peptide bond in peptides and proteins. J Mol Biol 264(5):1180–1195

    Article  CAS  Google Scholar 

  71. 71.

    Polavarapu PL, Deng ZY, Ewig CS (1994) Vibrational properties of the peptide group: achiral and chiral conformers of N-methylacetamide. J Phys Chem 98:9919–9930

    Article  CAS  Google Scholar 

  72. 72.

    Ramachandran GN (1968) Need for nonplanar peptide units in polypeptide chains. Biopolymers 6:1494–1496

    Article  CAS  Google Scholar 

  73. 73.

    Chakraborty TK, Kumar NVS, Roy S, Dutta SK, Kunwar AC, Sridhar B, Singh H (2011) Stereochemical control in the structures of linear δ, α-hybrid tripeptides containing tetrahydrofuran amino acids. J Phys Org Chem 24:720–731

    Article  CAS  Google Scholar 

  74. 74.

    Read AE, Weinstock RB, Weinhold F (1985) Natural population analysis. J Chem Phys 83:735

    Article  Google Scholar 

  75. 75.

    Ayers PW, Parr RG, Pearson RG (2006) Elucidating the hard/soft acid/base principle: a perspective based on half-reactions. J Chem Phys 124:194107

    Article  Google Scholar 

  76. 76.

    Mineva T, Sicilia E, Russo N (1998) Density-Functional approach to hardness evaluation and its use in the study of the maximum hardness principle. J Am Chem Soc 120:9053–9058

    Article  CAS  Google Scholar 

  77. 77.

    Luca GD, Sicilia E, Russo N, Mineva T (2002) On the hardness evaluation in solvent for neutral and charged systems. J Am Chem Soc 124:1494–1499

    Article  Google Scholar 

  78. 78.

    Fuentealba P, Simón-Manso Y, Chattaraj PK (2000) Molecular electronic excitations and the minimum polarizability principle. J Phys Chem A 104:3185–3187

    Article  CAS  Google Scholar 

  79. 79.

    Pearson RG (1997) Chemical hardness: applications from molecules to solids. Wiley-VCH, Weinheim

    Google Scholar 

  80. 80.

    Datta D (1992) "Hardness profile" of a reaction path. J Phys Chem 96:2409

    Article  CAS  Google Scholar 

  81. 81.

    Parr RG, Yang W (1989) Density functional theory of atoms and molecules. Oxford University Press, New York

    Google Scholar 

  82. 82.

    Chalmet S, Harb W, Ruiz-López MF (2001) Computer simulation of amide bond formation in aqueous solution. J Phys Chem A 105:11574–11581

    Article  CAS  Google Scholar 

  83. 83.

    Jensen F (2007) Introduction to computational chemistry, 2nd edn. Wiley, London

    Google Scholar 

  84. 84.

    Koch W, Holthausen MC (2001) A chemist’s guide to density functional theory. Wiley-VCH, New York

  85. 85.

    Jurečka P, Šponer J, Černý J, Hobza P (2006) Benchmark database of accurate (MP2 and CCSD(T) complete basis set limit) interaction energies of small model complexes, DNA base pairs, and amino acid pairs. Phys Chem Chem Phys 8:1985–1993

    Article  CAS  Google Scholar 

  86. 86.

    Cybulski SM, Lytle ML (2007) The origin of deficiency of the supermolecule second-order Møller-Plesset approach for evaluating interaction energies. J Chem Phys 127:141102

    Article  Google Scholar 

  87. 87.

    Nagarajam HA, Ramakrishnan C (1995) Stereochemical studies on cyclic peptides: detailed energy minimization studies on hydrogen bonded all-trans cyclic pentapeptide backbones. J Biosci 20:591–611

    Article  Google Scholar 

  88. 88.

    Hess BA, Schaad LJ (1971) Hueckel molecular orbital π resonance energies. The benzenoid hydrocarbons. J Am Chem Soc 93:2413–2416

    Article  CAS  Google Scholar 

  89. 89.

    Pearson RG (1988) Electronic spectra and chemical reactivity. J Am Chem Soc 110:2092–2097

    Article  CAS  Google Scholar 

  90. 90.

    Foresman JB, leen Frisch Æ (1996) exploring chemistry with electronic structure methods 2nd edn. Gaussian, Pittsburgh, PA

Download references

Acknowledgment

We thank the Department of Science and Technology, New Delhi, Government of India for financial support (SR/S1/OC01/2007).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Harjinder Singh.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 837 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kumar, N.V.S., Priyakumar, U.D., Singh, H. et al. Inter- versus intra-molecular cyclization of tripeptides containing tetrahydrofuran amino acids: a density functional theory study on kinetic control. J Mol Model 18, 3181–3197 (2012). https://doi.org/10.1007/s00894-011-1326-7

Download citation

Keywords

  • Peptides
  • Cyclization
  • Planarity
  • DFT
  • NBO