Advertisement

Amino Acids

, Volume 36, Issue 3, pp 563–569 | Cite as

Molecularly imprinted polymers for RGD selective recognition and separation

  • Emmanuel Papaioannou
  • Christos Koutsas
  • Maria Liakopoulou-KyriakidesEmail author
Original Article

Abstract

Molecularly imprinted polymers that could recognize the tripeptide Arg-Gly-Asp have been produced with the use of two functional monomers and three different cross-linkers, respectively. Methacrylic acid and acrylamide were used as functional monomers and the role of the ethylene glycol dimethacrylate, trimethylpropane trimethacrylate and N,N′-methylene-bisacrylamide as crosslinking monomers, was investigated on their recognition capability. The % net rebinding and the imprinting factor values were obtained, giving for the methacrylic acid–trimethylpropane trimethacrylate polymer the highest values 12.3% and 2.44, respectively. In addition, this polymer presented lower dissociation constant (K D) value and the higher B max% of theoretical total binding sites than all the other polymers. Rebinding experiments with Lys-Gly-Asp, an analogue of Arg-Gly-Asp, and other different peptides, such as cholecystokinin C-terminal tri- and pentapeptide and gramicidin, further indicated the selectivity of methacrylic acid-trimethylpropane trimethacrylate copolymer for Arg-Gly-Asp giving specific selectivity factor values 1.27, 1.98, 1.31 and 1.67, respectively.

Keywords

Arg-Gly-Asp RGD Copolymerization Molecular imprinting Radical polymerization 

Abbreviations

ABCN

Azo-bis-cyclohexane-carbonitrile

RGD

Arg-Gly-Asp tripeptide

KGD

Lys-Gly-Asp tripeptide

CCK-3, CCK-5

Cholecystokinin C-terminal tripeptide and pentapeptide, respectively

EGDMA

Ethylene glycol dimethacrylate

TRIM

Trimethylpropane trimethacrylate

MAA

Methacrylic acid

MIPs

Molecularly imprinted polymers

NIPs

Non imprinted polymers

SEM

Scanning electron microscopy

References

  1. Allender CJ, Brain KR, Heard CM (1997) Binding cross-reactivity of Boc-phenylalanine enantiomers on molecularly imprinted polymers. Chirality 9:233–237CrossRefGoogle Scholar
  2. Andersson LI, Müller R, Vlatakis G, Mosbach K (1995) Mimics of the binding sites of opioid receptors obtained by molecular imprinting of enkephalin and morphine. Proc Natl Acad Sci USA 92:4788–4792PubMedCrossRefGoogle Scholar
  3. Andersson LI, Müller R, Mosbach K (1996) Molecular imprinting of the endogenous neuropeptide Leu5-enkephalin and some derivatives thereof. Macromol Rapid Commun 17:65–71CrossRefGoogle Scholar
  4. Asanuma H, Akiyama T, Kajiya K, Hishiya T, Komiyama M (2001) Molecular imprinting of cyclodextrin in water for the recognition of nanometer-scaled guests. Anal Chim Acta 435:25–33CrossRefGoogle Scholar
  5. Basani RB, D’Andrea G, Mitra N, Vilaire G, Richbergs M, Kowalska MA, Bennet JS, Poncz M (2001) RGD-containing Peptides Inhibit Fibrinogen Binding to Platelet αIIbβ3 by Inducing an Allosteric Change in the Amino-terminal Portion of αIib. J Biol Chem 276:13975–13981PubMedGoogle Scholar
  6. Cheong SH, McNiven S, Rachkov A, Levi R, Yano K, Karube I (1997) Testosterone receptor binding mimic constructed using molecular imprinting. Macromolecules 30:1317–1322CrossRefGoogle Scholar
  7. Glad M, Norrlow O, Sellergren B, Siegbahn N, Mosbach K (1985) Use of silane monomers for molecular imprinting and enzyme entrapment in polysiloxane-coated porous silica. J Chromatogr 347:11–23CrossRefGoogle Scholar
  8. Kempe M (1996) Antibody-mimicking polymers as chiral stationary phases in HPLC. Anal Chem 68:1948–1953PubMedCrossRefGoogle Scholar
  9. Kempe M, Mosbach K (1995) Separation of amino acids, peptides and proteins on molecularly imprinted stationary phases. J Chromatogr A 691:317–323PubMedCrossRefGoogle Scholar
  10. Krlz D, Berggren Krlz C, Andersson LI, Mosbach K (1994) Thin-layer chromatography based on the molecular imprinting technique. Anal Chem 66:2636–2639CrossRefGoogle Scholar
  11. Komiyama M, Takeuchi T, Mukawa T, Asanuma H (2003) Molecular imprinting for fundamentals to applications. Wiley, VCHGoogle Scholar
  12. Lanza F, Sellergren B (2004) Molecularly imprinted polymers via high-throughput and combinatorial techniques. Macromol Rapid Commun 25:59–68CrossRefGoogle Scholar
  13. Liao JL, Wang Y, Hjertèn S (1996) A novel support with artificially created recognition for the selective removal of proteins and for affinity chromatography. Chromatographia 42:259–262CrossRefGoogle Scholar
  14. Mosbach K (1994) Molecular imprinting. Trends Biochem Sci 19:9–14PubMedCrossRefGoogle Scholar
  15. Mosbach K, Ramström O (1996) The emerging technique of molecular imprinting and its future impact on biotechnology. Biotechnology 14:163–170CrossRefGoogle Scholar
  16. Mosbach K, Haupt K (1998) Some new developments and challenges in noncovalent molecular imprinting technology. J Mol Recogn 2:62–68CrossRefGoogle Scholar
  17. Nishino H, Huang CS, Shea KJ (2006) Selective protein capture by epitope imprinting. Angew Chem Int Ed 45:2392–2396CrossRefGoogle Scholar
  18. Ojima I, Chakravarty S, Dong Q (1995) Antithrombotic agents: from RGD to peptide mimetics. Bioorg Med Chem 3:337–360PubMedCrossRefGoogle Scholar
  19. Papaioannou EH, Liakopoulou-Kyriakides M, Papi RM, Kyriakidis DA (2007) Molecularly imprinted polymers for cholecystokinin C-terminal pentapeptide. Macromol Chem Phys 208:2621–2627CrossRefGoogle Scholar
  20. Ramström O (2005) Synthesis and selection of functional and structural monomers. In: Ramström O, Yan M (eds) Molecularly imprinted materials: science and technology. Marcel Dekker, New YorkGoogle Scholar
  21. Ramström O, Nicholls IA, Mösbach K (1994) Synthetic peptide receptor mimics: highly stereoselective recognition in non-covalent molecularly imprinted polymers. Tetrah Asym 5:649–656CrossRefGoogle Scholar
  22. Sellergren B (2001) The non-covalent approach to molecular imprinting. In: Sellergren B (ed) Molecularly imprinted polymers: man-made mimics of antibodies and their applications in analytical chemistry. Elsevier Science BV, LondonGoogle Scholar
  23. Sellergren B, Lepisto M, Mosbach K (1988) Highly enantioselective and substrate-selective polymers obtained by molecular imprinting utilizing noncovalent interactions. NMR and chromatographic studies on the nature of recognition. J Am Chem Soc 110:5853–5860CrossRefGoogle Scholar
  24. Shea KJ, Spivak DA, Sellergren B (1993) Polymer complements to nucleotide bases. Selective binding of adenine derivatives to imprinted polymers. J Am Chem Soc 115:3368–3369CrossRefGoogle Scholar
  25. Wulff G (1995) Molecular imprinting in cross-linked materials with the aid of molecular templates-a way towards artificial antibodies. Angew Chem Int Ed Engl 34:1812–1832CrossRefGoogle Scholar
  26. Wulff G, Sarhan A, Zabrocki K (1973) Enzyme-analogue built polymers and their use for the resolution of racemates. Tetrahedron Lett 44:4329–4332CrossRefGoogle Scholar
  27. Yilmaz E, Schmidt RH, Mosbach K (2005) The noncovalent approach. In: Ramström O, Yan M (eds) Molecularly imprinted materials: science and technology. Marcel Dekker, New YorkGoogle Scholar
  28. Ye L, Ramström O, Mosbach K (1998) Molecularly imprinted polymeric adsorbents for byproduct removal. Anal Chem 70:2789–2795CrossRefGoogle Scholar
  29. Ye L, Weiss R, Mosbach K (2000) Synthesis and characterization of molecularly imprinted microspheres. Macromolecules 33:8239–8245CrossRefGoogle Scholar
  30. Yu C, Mosbach K (1997) Molecular imprinting utilizing an amide functional group for hydrogen bonding leading to highly efficient polymers. J Org Chem 62:4057–4064CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Emmanuel Papaioannou
    • 1
  • Christos Koutsas
    • 1
  • Maria Liakopoulou-Kyriakides
    • 1
    Email author
  1. 1.Section of Chemistry, Faculty of Chemical EngineeringAristotle University of ThessalonikiThessalonikiGreece

Personalised recommendations