Amino Acids

, Volume 10, Issue 4, pp 295–304 | Cite as

Differential self assembly of amphiphilic helical peptides

  • R. Lutgring
  • M. Lipton
  • J. Chmielewski
Article

Summary

A series of amphiphilic, helical peptides was designed and synthesized to investigate the components necessary for formation of helical bundles with differing aggregation states. Minimalistic sequences were employed for the peptides which contained either four (Leu4), six (Leu6) or eight (Leu8) leucine residues within a sixteen amino acid sequence. All peptides were highly helical as evaluated by circular dichroism, and the helical content of each peptide exhibited a concentration dependence. Size exclusion chromatography confirmed aggregation states of dimer/trimer forLeu4, tetramer forLeu6, and hexamer octamer forLeu8. Disulfide crosslinking studies also confirmed that the dimer ofLeu4 favored a parallel orientation with respect to the helical dipole. This systematic study clearly defines the role of hydrophobicity in the self assembly of helical peptides; peptides with a small hydrophobic face favor small bundle sizes, whereas peptides containing larger hydrophobic faces form correspondingly larger helical bundles.

Keywords

Amino acids Self assembly Peptide Amphiphilic Helical 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akerfeldt KS, Kim RM, Camac D, Groves JT, Lear JD, DeGrado WF (1992) Tetraphilin: a four-helix proton channel built on a tetraphenylporphyrin framework. J Am Chem Soc 114: 9656–9658Google Scholar
  2. Chang CD, Meienhofer J (1978) Solid-phase synthesis using mild base cleavage of N-fluorenylmethyloxycarbonylamino acids. Int J Pept Protein Res 11: 246–249Google Scholar
  3. Chin TM, Berndt KD, Yang N (1992) Self-assembling hexameric helical bundle forming peptides. J Am Chem Soc 114: 2279–2280Google Scholar
  4. Chmielewski J, Lipton M (1994) The rational design of highly stable, amphiphilic helical peptides. Int J Pept Protein Res 44: 152–157Google Scholar
  5. Chou PY, Fasman GD (1974) Conformational parameters for amino acids in helical,β-sheet and random coil regions calculated from proteins. Biochemistry 13: 211–225Google Scholar
  6. Crick FHC (1953) The packing ofα-helices: simple coiled coils. Acta Crystallogr 6: 689–697Google Scholar
  7. Eisenberg D, Wilcox W, Eshita SM, Pryciak PM, Ho SP, DeGrado WF (1986) The design, synthesis and crystallization of an alpha-helical peptide. Proteins 1: 16–22Google Scholar
  8. Ghadiri RM, Soares C, Choi C (1992) Design of an artificial four-helix bundle metalloprotein via a novel ruthenium(II)-assisted self-assembly process. J Am Chem Soc 114: 4000–4002Google Scholar
  9. Harbury PB, Kim PS, Alber T (1994) Crystal structure of an isoleucine-Zipper trimer. Nature 371: 80–83Google Scholar
  10. Hecht MH, Richardson JS, Richardson DC, Ogden RC (1990) De novo design, expression and characterization of felix: a four-helix bundle protein of native-like sequence. Science 249: 884–892Google Scholar
  11. Ho SP, DeGrado WF (1987) Design of a 4-helix bundle protein: synthesis of peptides which self-associated into a helical protein. J Am Chem Soc 109: 6751–6758Google Scholar
  12. Lau S, Taneja AK, Hodges RS (1984) Synthesis of a model protein of defined secondary and tertiary structure. J Biol Chem 259: 13253–13261Google Scholar
  13. Lieberman M, Sasaki T (1991) Iron(II) organizes a synthetic peptide inti three-helix bundles. J Am Chem Soc 113: 1470–1471Google Scholar
  14. Lyu PC, Sherman JC, Chen A, Kallenbach NR (1991)α-Helix stabilization by natural and unnatural amino acids with alkyl sidechains. Proc Natl Acad Sci USA 88: 5317–5320Google Scholar
  15. Monera OD, Kay CM, Hodges RS (1994) Electrostatic interactions control the parallel and antiparallel orientation ofα-helical chains in two-strandedα-helical coiled coils. Biochemistry 33: 3862–3871Google Scholar
  16. Monera OD, Zhou NE, Kay CM, Hodges RS (1993) Comparison of parallel and antiparallel two-standedα-helical coiled coils. J Biol Chem 268: 19218–19227Google Scholar
  17. Mosjov S, Merrifield RB (1981) Solid phase synthesis of crystalline glucagon. Biochemistry 20: 2950–2956Google Scholar
  18. Mutter M, Tuchscherer GG, Miller C, Altmann KH, Carey RI, Wyss DF, Labhardt AM, Rivier JE (1992) Template-assisted synthetic proteins with four-helix bundle topology. J Am Chem Soc 114: 1463–1470Google Scholar
  19. O'Shea EK, Klemm JD, Kim PS, Alber T (1991) X-ray structure of the GCN4 leucine Zipper, a two-stranded, parallel coiled coil. Science 254: 539–544Google Scholar
  20. Osterhout JJ, Handel T, Na G, Toumadje A, Long RC, Connolly RJ, Hoch JC, Johnson WC, Live D, DeGrado WF (1992) Characterization of the structural properties ofα1B, a peptide designed to form a four-helix bundle. J Am Chem Soc 114: 331–337Google Scholar
  21. Rink H (1987) Solid-phase synthesis of protected peptide tragments using trialkoxydiphenyl-methyl ester resin. Tetrahedron Lett 28: 3787–3790Google Scholar
  22. Sasaki T, Kaiser ET (1989) Helichrome: synthesis and enzymatic activity of a designed hemeprotein. J Am Chem Soc 111: 380–381Google Scholar
  23. Scheraga HA (1978) Use of random copolymers to detemine the helix-coil stability constants of the naturally occurring amino acids. Pure Appl Chem 50: 315–324Google Scholar
  24. Shoemaker KR, Kim PS, Brems DN, Marqusee S, York EJ, Chaiken IM, Stewart JM, Baldwin RL (1985) Nature of the charged-group effect on the stability of the C-peptide helix. Proc Natl Acad Sci USA 82: 2349–2353Google Scholar
  25. Shoemaker KR, Kim PS, York EJ, Stewart JM, Baldwin RL (1987) Tests of the helix dipole model for stabilization ofα-helices. Nature 326: 563–567Google Scholar
  26. Zhou NE, Kay CM, Hodges RS (1992) Synthetic model proteins. J Biol Chem 267: 2664–2670Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • R. Lutgring
    • 1
  • M. Lipton
    • 2
  • J. Chmielewski
    • 2
  1. 1.Department of ChemistryUniversity of EvansvilleEvansvilleUSA
  2. 2.Department of ChemistryPurdue UniversityWest LafayetteUSA

Personalised recommendations