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The interaction of La3+ complexes of DOTA/DTPA glycoconjugates with the RCA120 lectin: a saturation transfer difference NMR spectroscopic study

  • João M. C. Teixeira
  • David M. Dias
  • F. Javier Cañada
  • José A. Martins
  • João P. André
  • Jesús Jiménez-Barbero
  • Carlos F. G. C. GeraldesEmail author
Original Paper

Abstract

The study of ligand–receptor interactions using high-resolution NMR techniques, namely the saturation transfer difference (STD), is presented for the recognition process between La(III) complexes of 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane monoamide and diethylenetriaminepentaacetic acid bisamide glycoconjugates and the galactose-specific lectin Ricinus communis agglutinin (RCA120). This new class of Gd(III)-based potential targeted MRI contrast agents (CAs), bearing one or two terminal sugar (galactosyl or lactosyl) moieties, has been designed for in vivo binding to the asialoglycoprotein receptor, which is specifically expressed at the surface of liver hepatocytes, with the aim of leading to a new possible diagnosis of liver diseases. The in vitro affinity constants for the affinity of the divalent La(III)–glycoconjugate complexes for RCA120, used as a simple, water-soluble receptor model, were higher than those of the monovalent analogues. The combination of the experimental data obtained from the STD NMR experiments with molecular modelling protocols (Autodock 4.1) allowed us to predict the mode of binding of monovalent and divalent forms of these CAs to the galactose 1α binding sites of RCA120. The atomic details of the molecular interactions allowed us to corroborate and supported the interaction of both sugar moieties and the linkers with the surface of the protein and, thus, their contribution to the observed interaction stabilities.

Keywords

Ligand–receptor binding Glycoconjugates Saturation transfer difference NMR spectroscopy MRI contrast agents Protein–ligand interaction 

Notes

Acknowledgments

This work was supported by the Fundação para a Ciência e a Tecnologia (FCT), Portugal (project PTDC/QUI/70063/2006) and FEDER. The Varian VNMRS 600 MHz NMR spectrometer in Coimbra was acquired with the support of the Programa Nacional de Reequipamento Científico of FCT, Portugal, contract REDE/1517/RMN/2005—as part of Rede Nacional de RMN (RNRMN). This work was carried out in the framework of the COST D38 Action. The group in Madrid thanks the Ministery of Science and Innovation of Spain for financial support (grant CTQ2009-08536). We also thank Eurico Cabrita for useful discussions.

References

  1. 1.
    Engvall E, Perlmann P (1971) Immunochemistry 8:871–874PubMedCrossRefGoogle Scholar
  2. 2.
    Yalow BRS, Berson SA (1960) J Clin Invest 39:11–13CrossRefGoogle Scholar
  3. 3.
    Cuatrecasas P, Wilchek M, Anfinsen CB (1968) Biochemistry 61:636–643Google Scholar
  4. 4.
    Homola J, Yee SS, Gauglitz G (1999) Sens Actuators B Chem 54:3–15CrossRefGoogle Scholar
  5. 5.
    Meyer B, Peters T (2003) Angew Chem Int Ed 42:864–890CrossRefGoogle Scholar
  6. 6.
    Ni F (1994) Progr Nucl Magn Reson Spectrosc 26:517–606CrossRefGoogle Scholar
  7. 7.
    Chen A, Shapiro MJ (1998) J Am Chem Soc 120:10258–10259CrossRefGoogle Scholar
  8. 8.
    Dalvit C, Pevarello P, Tatò M, Veronesi M, Vulpetti A, Sundström M (2000) J Biomol NMR 18:65–68PubMedCrossRefGoogle Scholar
  9. 9.
    Dalvit C, Fogliatto G, Stewart A, Veronesi M, Stockman B (2001) J Biomol NMR 21:349–359PubMedCrossRefGoogle Scholar
  10. 10.
    Mayer M, Meyer B (1999) Angew Chem Int Ed 38:1784–1788CrossRefGoogle Scholar
  11. 11.
    Vogtherr M, Peters T (2000) J Am Chem Soc 122:6093–6099CrossRefGoogle Scholar
  12. 12.
    Mayer M, Meyer B (2001) J Am Chem Soc 123:6108–6117PubMedCrossRefGoogle Scholar
  13. 13.
    Lepre C, Moore JM, Peng JW (2004) Chem Rev 104:3641–3676PubMedCrossRefGoogle Scholar
  14. 14.
    Fielding L (2007) Progr Nucl Magn Reson Spectrosc 51:219–242CrossRefGoogle Scholar
  15. 15.
    Meinecke R, Meyer B (2001) J Med Chem 44:3059–3065PubMedCrossRefGoogle Scholar
  16. 16.
    Neffe AT, Bilang M, Grüneberg I, Meyer B (2007) J Med Chem 50:3482–3488PubMedCrossRefGoogle Scholar
  17. 17.
    Angulo J, Enríquez-Navas PM, Nieto PM (2010) Chem Eur J 16:7803–7812CrossRefGoogle Scholar
  18. 18.
    Hajduk PJ, Mack JC, Olejniczak ET, Park C, Dandliker PJ, Beutel B (2004) J Am Chem Soc 126:2390–2398PubMedCrossRefGoogle Scholar
  19. 19.
    Klein J, Meinecke R, Mayer M, Meyer B (1999) J Am Chem Soc 121:5336–5337CrossRefGoogle Scholar
  20. 20.
    Kolympadi M, Fontanella M, Venturi C, André S, Gabius H-J, Jiménez-Barbero J, Vogel P (2009) Chem Eur J 15:2861–2873CrossRefGoogle Scholar
  21. 21.
    Jiménez-Barbero J, Dragoni E, Venturi C, Nannucci F, Ardá A, Fontanella M, André S, Cañada FJ, Gabius H-J, Nativi C (2009) Chem Eur J 15:10423–10431CrossRefGoogle Scholar
  22. 22.
    Leffler H, Carlsson S, Hedlund M, Qian Y, Poirier F (2004) Glycoconj J 19:433–440PubMedCrossRefGoogle Scholar
  23. 23.
    Almkvist J, Karlsson A (2004) Glycoconj J 19:575–581PubMedCrossRefGoogle Scholar
  24. 24.
    Critchley P, Willand MN, Rullay AK, Crout DH (2003) Org Biomol Chem 1:928–938PubMedCrossRefGoogle Scholar
  25. 25.
    Ashwell G, Harford J (1982) Ann Rev Biochem 51:531–544PubMedCrossRefGoogle Scholar
  26. 26.
    André JP, Geraldes CFGC, Martins JA, Merbach AE, Prata MIM, Santos AC, de Lima JJP, Tóth E (2004) Chem Eur J 10:5804–5816Google Scholar
  27. 27.
    Baía P, André JP, Geraldes CFGC, Martins JA, Merbach AE, Tóth E (2005) Eur J Inorg Chem 2110–2119Google Scholar
  28. 28.
    Fulton DA, Elemento EM, Aime S, Chaabane L, Botta M, Parker D (2006) Chem Commun 1064–1066Google Scholar
  29. 29.
    Lee YC (1992) FASEB J 6:3193–3200PubMedGoogle Scholar
  30. 30.
    Lee RT, Lee YC (2001) Glycoconj J 17:543–551CrossRefGoogle Scholar
  31. 31.
    Lundquist J, Toone EJ (2002) Chem Rev 102:555–578PubMedCrossRefGoogle Scholar
  32. 32.
    Lee YC, Lee RT (1995) Acc Chem Res 28:321–327CrossRefGoogle Scholar
  33. 33.
    Lee YC, Townsend RR, Hardy MR, Lönngren J, Arnarp J, Haraldsson M, Lönn H (1983) J Biol Chem 258:199–202PubMedGoogle Scholar
  34. 34.
    Biessen EA, Broxterman H, van Boom JH, van Berkel TJ (1995) J Med Chem 38:1846–1852PubMedCrossRefGoogle Scholar
  35. 35.
    Lundquist JJ, Debenham SD, Toone EJ (2000) J Org Chem 65:8245–8250PubMedCrossRefGoogle Scholar
  36. 36.
    Corbell J (2000) Tetrahedron Asymmetry 11:95–111CrossRefGoogle Scholar
  37. 37.
    Meier M, Bider MD, Malashkevich VN, Spiess M, Burkhard P (2000) J Mol Biol 300:857–865PubMedCrossRefGoogle Scholar
  38. 38.
    Nahálková J, Svitel J, Gemeiner P, Danielsson P, Pribulová B, Petrus L (2002) J Biochem Biophys Methods 52:11–18PubMedCrossRefGoogle Scholar
  39. 39.
    D’Agata R, Grasso G, Iacono G, Spoto G, Vecchio G (2006) Org Biomol Chem 4:610–612PubMedCrossRefGoogle Scholar
  40. 40.
    Lee M, Park S, Shin I (2006) Bioorg Med Chem Lett 16:5132–5135PubMedCrossRefGoogle Scholar
  41. 41.
    Nicolson GL, Blaustein J, Etzler ME (1974) Biochemistry 13:196–204PubMedCrossRefGoogle Scholar
  42. 42.
    Olsnes S, Saltvedt E, Pihl A (1974) J Biol Chem 249:803–810PubMedGoogle Scholar
  43. 43.
    Endo Y, Tsurugi K (1987) J Biol Chem 262:8128–8130PubMedGoogle Scholar
  44. 44.
    Lamb FI, Roberts LM, Lord JM (1985) Eur J Biochem 148:265–270PubMedCrossRefGoogle Scholar
  45. 45.
    Houston LL, Dooley TP (1982) J Biol Chem 257:4147–4151PubMedGoogle Scholar
  46. 46.
    Sharma S, Bharadwaj S, Surolia A, Podder SK (1998) Biochem J 333(3):539–542PubMedGoogle Scholar
  47. 47.
    Dam TK, Brewer CF (2002) Chem Rev 102:387–429PubMedCrossRefGoogle Scholar
  48. 48.
    Sphyris N, Lord JM, Wales R, Roberts LM (1995) J Biol Chem 270:20292–20297PubMedCrossRefGoogle Scholar
  49. 49.
    Rivera-Sagredo A, Jiménez-Barbero J, Martín-Lomas M, Solís D, Díaz-Mauriño T (1992) Carbohydr Res 232:207–226PubMedCrossRefGoogle Scholar
  50. 50.
    Hwang T-L, Shaka AJ (1995) J Magn Reson A 112:275–279CrossRefGoogle Scholar
  51. 51.
    Goodsell DS, Morris GM, Olson AJ (1996) J Mol Recognit 9:1–5PubMedCrossRefGoogle Scholar
  52. 52.
    Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) J Comput Chem 19:1639–1662CrossRefGoogle Scholar
  53. 53.
    Schrödinger (2008) Maestro, version 8.5. Schrödinger, New YorkGoogle Scholar
  54. 54.
    Prata MIM, Santos AC, Torres S, André JP, Martins JA, Neves M, García-Martín ML, Rodrigues TB, López-Larrubia P, Cerdán S, Geraldes CFGC (2006) Contrast Med Mol Imaging 258:246–258CrossRefGoogle Scholar
  55. 55.
    Kanai M, Mortell KH, Kiessling LL (1997) J Am Chem Soc 119:9931–9932CrossRefGoogle Scholar
  56. 56.
    Kramer RH, Karpen JW (1998) Nature 395:710–713PubMedCrossRefGoogle Scholar
  57. 57.
    Bernardi A, Arosio D, Potenza D, Sánchez-Medina I, Mari S, Cañada FJ, Jiménez-Barbero J (2004) Chem Eur J 10:4395CrossRefGoogle Scholar
  58. 58.
    Terraneo G, Potenza D, Canales A, Jiménez-Barbero J, Baldridge KK, Bernardi A (2007) J Am Chem Soc 129:2890–2900PubMedCrossRefGoogle Scholar

Copyright information

© SBIC 2011

Authors and Affiliations

  • João M. C. Teixeira
    • 1
  • David M. Dias
    • 1
  • F. Javier Cañada
    • 2
  • José A. Martins
    • 3
  • João P. André
    • 3
  • Jesús Jiménez-Barbero
    • 2
  • Carlos F. G. C. Geraldes
    • 1
    Email author
  1. 1.Department of Life Sciences, Faculty of Science and Technology, Center of Neurosciences and Cell BiologyUniversity of CoimbraCoimbraPortugal
  2. 2.Department of Chemical and Physical BiologyCIB-CSICMadridSpain
  3. 3.Centro de Química, Campus de GualtarUniversidade do MinhoBragaPortugal

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