European Food Research and Technology

, Volume 219, Issue 6, pp 579–583 | Cite as

Quantitative structure-activity relationship modelling of ACE-inhibitory peptides derived from milk proteins

  • Are Hugo Pripp
  • Tomas Isaksson
  • Leszek Stepaniak
  • Terje Sørhaug
Original Paper

Abstract

Quantitative structure-activity relationship (QSAR) modelling was performed on peptides derived from milk proteins that inhibit angiotensin-I-converting enzyme (ACE). Physico-chemical descriptors expressed hydrophobicity, size and charge of side chains of the two most external amino acids in N- or C-terminal position. Models were estimated with partial least squares regression and validated with full cross-validation. A relationship (R=0.73, p<0.001) was found between hydrophobicity and positively charged amino acid in C-terminal position, size of amino acid next to C-terminal position and ACE-inhibition of peptides up to six amino acids in length. When longer peptides were included the relationship between C-terminal structure and activity decreased, reflecting the likely influence by steric effects. No relationship between N-terminal structure and inhibition activity was found. These biochemical interpretations were supported by findings from QSAR-modelling using so-called z-scales developed by Jonsson et al. (1989, Quant. Struct.-Act Relat. 8, 204–209) for amino acids.

Keywords

QSAR ACE-inhibition Peptides Milk proteins 

References

  1. 1.
    Wyvratt MJ, Patchet AA (1985) Med Res Rev 5:485–531Google Scholar
  2. 2.
    Fitzgerald RJ, Meisel A (2003) Milk protein hydrolysates and bioactive peptides. In: Fox PF, McSweeney PLH (eds) Advanced dairy chemistry, vol 1, proteins, 3rd edn. Kluwer Academic/Plenum Publishers, New York, pp 675–698Google Scholar
  3. 3.
    Gobbetti M, Stepaniak L, De Angelis M, Corsetti A, Di Cagno R (2002) Crit Rev Food Sci 42:223–239Google Scholar
  4. 4.
    Esbensen KH (2001) Multivariate data analysis—in practice. Camo Process AS, Oslo, NorwayGoogle Scholar
  5. 5.
    Jonsson JM, Eriksson L, Hellberg S, Sjöström M, Wold S (1989) Quant Struct–Act Relat 8:204–209Google Scholar
  6. 6.
    Hellberg S, Sjöström M, Skagerberg B, Wold S (1987) J Med Chem 30:1126–1135PubMedGoogle Scholar
  7. 7.
    Hellberg S, Eriksson L, Jonsson J, Lindgren F, Sjöström M, Skagerberg B, Wold S, Andrews P (1991) Int J Pept Protein Res 37:414–424PubMedGoogle Scholar
  8. 8.
    Martens M, Martens H (1986) Appl Spectrosc 40:303–310Google Scholar
  9. 9.
    Martens H, Naes T (1987) Multivariate calibration by data compression. In: Williams PC, Norris K (ed) Near-infrared technology in the agricultural and food industries. Assoc Cer Chem, St. Paul, pp 57–87Google Scholar
  10. 10.
    Sollie LA (2003) Bioactive peptides in fish. MSc Thesis, Agricultural University of NorwayGoogle Scholar
  11. 11.
    Martens H, Martens M (2000) Food Qual Pref 11:5–16CrossRefGoogle Scholar
  12. 12.
    Cheung HS, Feng-Lai W, Ondetti MA, Sabo EF, Cushman DW (1980) J Biol Chem 255:401–407PubMedGoogle Scholar
  13. 13.
    Ondetti MA, Cushman DW (1982) Ann Rev Biochem 51:283–308CrossRefPubMedGoogle Scholar
  14. 14.
    Hopp TP, Woods KR (1981) Proc Natl Acad Sci USA 78:3824–3828PubMedGoogle Scholar
  15. 15.
    Kyte J, Doolittle R (1982) J Mol Biol 157:105–132PubMedGoogle Scholar
  16. 16.
    Cheftel JC, Cuq J-L, Lorient D (1985) Amino acids, peptides and proteins. In: Fennema OR (ed) Food chemistry. Marcel Dekker Inc, New York, pp 245–367Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Are Hugo Pripp
    • 1
  • Tomas Isaksson
    • 1
  • Leszek Stepaniak
    • 1
  • Terje Sørhaug
    • 1
  1. 1.Department of Chemistry, Biotechnology and Food ScienceAgricultural University of NorwayÅsNorway

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