Skip to main content
SpringerLink
Log in

In vivo kinetics and biodistribution analysis of neoglycoproteins: effects of chemically introduced glycans on proteins

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Biodistribution and in vivo kinetics analysis of chemically prepared neoglycoproteins are reviewed. Various mono- and oligosaccharides were conjugated onto the protein surface by use of chemical methods. Their kinetic and organ-specific accumulation have extensively been studied after intravenous injection and analyzed by conventional dissection studies, as well as noninvasive methods, such as SPECT, PET, or fluorescence imaging. These studies clearly show the glycan-structure dependency on protein kinetics, which will provide promising possibilities for pharmacological and diagnostic applications.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kamerling, J.P., Boons, G.-J., Lee, Y.C., Suzuki, A., Taniguchi, N., Voragen, A.G.J. (eds.): Analysis of Glycans, Polysaccharide Functional Properties & Biochemistry of Glycoconjugate Glycans, Carbohydrate-mediated Interactions. In: Comprehensive Glycoscience, From Chemistry to Systems Biology, Vol II & III. Elsevier, UK (2007)

  2. Morell, A.G., Irvine, R.A., Sternlieb, I., Scheinberg, I.H., Ashwell, G.: Physical and chemical studies on ceruloplasmin. V. Metabolic studies on sialic acid-free ceruloplasmin in vivo. J. Biol. Chem. 243, 155–159 (1968)

    CAS  PubMed  Google Scholar 

  3. Elliott, S., Lorenzini, T., Asher, S., Aoki, K., Brankow, D., Buck, L., Busse, L., Chang, D., Fuller, J., Grant, J., Hernday, N., Hokum, M., Hu, S., Knudten, A., Levin, N., Komorowski, R., Martin, F., Navarro, R., Osslund, T., Rogers, G., Rogers, N., Trail, G., Egrie, J.: Enhancement of therapeutic protein in vivo activities through glycoengineering. Nat. Biotechnol. 21, 414–421 (2003)

    Article  CAS  PubMed  Google Scholar 

  4. Sato, M., Furuike, T., Sadamoto, R., Fujitani, N., Nakahara, T., Niikura, K., Monde, K., Kondo, H., Nishimura, S.I.: Glycoinsulins: dendritic sialyloligosaccharide-displaying insulins showing a prolonged blood-sugar-lowering activity. J. Am. Chem. Soc. 126, 14013–14022 (2004)

    Article  CAS  PubMed  Google Scholar 

  5. Kaneko, Y., Nimmerjahn, F., Ravetch, J.V.: Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313, 670–673 (2006)

    Article  CAS  PubMed  Google Scholar 

  6. Tanaka, K., Fukase, K.: PET (positron emission tomography) imaging of biomolecules using metal/DOTA complexes: a new collaborative challenge by chemists, biologists, and physicians for future diagnostics and exploration of in vivo dynamics. Org. Biomol. Chem. 6, 815–828 (2008)

    Article  CAS  PubMed  Google Scholar 

  7. Vyas, S.P., Singh, A., Sihorkar, V.: Ligand-receptor-mediated drug delivery: an emerging paradigm in cellular drug targeting. Crit. Rev. Ther. Drug Carrier Syst. 18, 1–76 (2001)

    Article  CAS  PubMed  Google Scholar 

  8. Willis, M., Forssen, E.: Ligand-targeted liposomes. Adv. Drug Deliv. Rev. 29, 249–271 (1998)

    Article  PubMed  Google Scholar 

  9. Fukase, K., Tanaka, K.: Bio-imaging and cancer targeting with glycoproteins and N-glycans. Curr. Opin. Chem. Biol. 16, 614–621 (2012). and references cited therein

    Article  CAS  PubMed  Google Scholar 

  10. Jain, K., Kesharwani, P., Gupta, U., Jain, N.K.: A review of glycosylated carriers for drug delivery. Biomaterials 33, 4166–4186 (2012)

    Article  CAS  PubMed  Google Scholar 

  11. Lee, Y.C., Stowell, C.P., Krantz, M.J.: 2-Imino-2-methoxyethyl 1-thioglycosides: new reagents for attaching sugars to proteins. Biochemistry 15, 3956–3963 (1976)

    Article  CAS  PubMed  Google Scholar 

  12. Gray, G.R.: The direct coupling of oligosaccharides to proteins and derivatized gels. Arch. Biochem. Biophys. 163, 426–428 (1974)

    Article  CAS  PubMed  Google Scholar 

  13. Kojima, S., Ishido, M., Kubota, K., Kubodera, A., Hellmann, T., Kohnke-Godt, B., Wosgien, B., Gabius, H.-J.: Tissue distribution of radioiodinated neoglycoproteins and mammalian lectins. Biol. Chem. Hoppe-Seyler 371, 331–338 (1990)

    Article  CAS  PubMed  Google Scholar 

  14. Ashwell, G., Harford, J.: Carbohydrate-specific receptors of the liver. Annu. Rev. Biochem. 51, 531–554 (1982)

    Article  CAS  PubMed  Google Scholar 

  15. Nishikawa, M., Hirabayashi, H., Takakura, Y., Hashida, M.: Design for cell-specific targeting of proteins utilizing sugar-recognition mechanism: effect of molecular weight of proteins on targeting efficiency. Pharm. Res. 12, 209–214 (1995)

    Article  CAS  PubMed  Google Scholar 

  16. Nishikawa, M., Miyazaki, C., Yamashita, F., Takakura, Y., Hashida, M.: Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties. Am. J. Physiol. 268, G849–G856 (1995)

    CAS  PubMed  Google Scholar 

  17. Gunn, A.J., Hama, Y., Koyama, Y., Kohn, E.C., Choyke, P.L., Kobayashi, H.: Targeted optical fluorescence imaging of human ovarian adenocarcinoma using a galactosyl serum albumin-conjugated fluorophore. Cancer Sci. 98, 1727–1733 (2007)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Hama, Y., Urano, Y., Koyama, Y., Choyke, P.L., Kobayashi, H.: D-galactose receptor-targated in vivo spectral fluorescence imaging of peritoneal metastasis using galactosamin-conjugated serum albumin-rhodamine green. J. Biomed. Opt. 12, 051501 (2007)

    Article  PubMed  Google Scholar 

  19. Regino, C.A.S., Ogawa, M., Alford, R., Wong, K.J., Kosaka, N., Williams, M., Feild, B.J., Takahashi, M., Choyke, P.L., Kobayashi, H.: Two-step synthesis of galactosylated human serum albumin as a targeted optical imaging agent for peritoneal carcinomatosis. J. Med. Chem. 53, 1579–1586 (2010)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Chopra, A.: [99mTc]-diethylenetriaminepentaacetic acid-galactosyl human serum albumin. 2007 Apr 24 [Updated 2007 Jun 12]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK23514/

  21. Stahl, P.D., Wileman, T.E., Diment, S., Shepherd, V.L.: Mannose-specific oligosaccharide recognition by mononuclear phagocytes. Biol. Cell. 51, 215–218 (1984)

    Article  CAS  PubMed  Google Scholar 

  22. Doebber, T.W., Wu, M.S., Bugianesi, R.L., Ponpipom, M.M., Furbish, F.S., Barranger, J.A., Brady, R.O., Shen, T.Y.: Enhanced macrophage uptake of synthetically glycosylated human placental β-glucocerebrosidase. J. Biol. Chem. 257, 2193–2199 (1982)

    CAS  PubMed  Google Scholar 

  23. Takagi, K., Uehara, T., Kaneko, E., Nakayama, M., Koizumi, M., Endo, K., Arano, Y.: 99mTc-labeled mannosyl-neoglycoalbumin for sentinel lymph node identification. Nucl. Med. Biol. 31, 893–900 (2004)

    Article  CAS  PubMed  Google Scholar 

  24. Jeong, J.M., Hong, M.K., Kim, Y.J., Lee, J., Kang, J.H., Lee, D.S., Chung, J.-K., Lee, M.C.: Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging. Nucl. Med. Commun. 25, 1211–1217 (2004)

    Article  CAS  PubMed  Google Scholar 

  25. Yabe, Y., Nishikawa, M., Tamada, A., Takakura, Y., Hashida, M.: Targeted delivery and improved therapeutic potential of catalase by chemical modification: combination with superoxide dismutase derivatives. J. Pharmacol. Exper. Ther. 289, 1176–1184 (1999)

    CAS  Google Scholar 

  26. Yabe, Y., Kobayashi, N., Nishikawa, M., Mihara, K., Yamashita, F., Takakura, Y., Hashida, M.: Pharmacokinetics and preventive effects of targeted catalase derivatives on hydrogen peroxide-induced injury in perfused rat liver. Pharm. Res. 19, 1815–1821 (2002)

    Article  CAS  PubMed  Google Scholar 

  27. Opanasopit, P., Nishikawa, M., Yamashita, F., Takakura, Y., Hashida, M.: Pharmacokinetic analysis of lectin-dependent biodistribution of fucosylated bovine serum albumin: a possible carrier for Kupffer cells. J. Drug Target. 9, 341–351 (2001)

    Article  CAS  PubMed  Google Scholar 

  28. Sarkar, K., Sarkar, H.S., Kole, L., Das, P.K.: Receptor-mediated endocytosis of fucosylated neoglycoprotein by macrophages. Mol. Cell. Biochem. 156, 109–116 (1996)

    Article  CAS  PubMed  Google Scholar 

  29. Kim, S., Jeong, J.M., Hong, M.K., Jang, J.-J., Lee, J., Lee, D.S., Chung, J.-K., Lee, M.C.: Differential receptor targeting of liver cells using 99mTc-neoglycosylated human serum albumins. Arch. Pharm. Res. 31, 60–66 (2008)

    Article  CAS  PubMed  Google Scholar 

  30. Choi, J.Y., Jeong, J.M., Yoo, B.C., Kim, K., Kim, Y., Yang, B.Y., Lee, Y.-S., Lee, D.S., Chung, J.-K., Lee, M.C.: Development of 68Ga-labeled mannosylated human serum albumin (MSA) as a lymph node imaging agent for positron emission tomography. Nucl. Med. Biol. 38, 371–379 (2011)

    Article  CAS  PubMed  Google Scholar 

  31. McCann, T.E., Kosaka, N., Mitsunaga, M., Choyke, P.L., Gildersleeve, J.C., Kobayashi, H.: Biodistribution and excretion of monosaccharides-albumin conjugates measured with in vivo near infrared fluorescence imaging. Bioconjug. Chem. 21, 1925–1932 (2010)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Alexander, V.M., Sano, K., Yu, Z., Nakajima, T., Choyke, P.L., Ptaszek, M., Kobayashi, H.: Galactosyl human serum albumin-NMP1 conjugate: a near infrared (NIR)-activatable fluorescence imaging agent to detect peritoneal ovarian cancer metastases. Bioconjug. Chem. 23, 1671–1679 (2012)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Lehrman, M.A., Pizzo, S.V., Imber, M.J., Hill, R.L.: The binding of fucose-containing glycoproteins by hepatic lectins. J. Biol. Chem. 261, 7412–7418 (1986)

    CAS  PubMed  Google Scholar 

  34. André, S., Unverzagt, C., Kojima, S., Dong, X., Fink, C., Kayser, K., Gabius, H.-J.: Neoglycoproteins with the synthetic complex biantennary nonasaccharide or its α2,3/α2,6-sialylated derivatives: their preparation, assessment of their ligand properties for purified lectins, for tumor cells in vitro, and in tissue sections, and their biodistribution in tumor-bearing mice. Bioconjug. Chem. 8, 845–855 (1997)

    Article  PubMed  Google Scholar 

  35. Unverzagt, C., André, S., Seifert, J., Kojima, S., Fink, C., Srikrishna, G., Freeze, H., Kayser, K., Gabius, H.-J.: Structure-activity profiles of complex biantennary glycans with core fucosylation and with/without additional α2,3/α2,6 sialylation: synthesis of neoglycoproteins and their properties in lectin assays, cell binding, and organ uptake. J. Med. Chem. 45, 478–491 (2002)

    Article  CAS  PubMed  Google Scholar 

  36. André, S., Unverzagt, C., Kojima, S., Frank, M., Seifert, J., Fink, C., Kayser, K., von der Lieth, C.-W., Gabius, H.-J.: Determination of modulation of ligand properties of synthetic complex-type biantennary N-glycans by introduction of bisecting GlcNAc in silico, in vitro and in vivo. Eur. J. Biochem. 271, 118–134 (2004)

    Article  PubMed  Google Scholar 

  37. André, S., Kojima, S., Prahl, I., Lensch, M., Unverzagt, C., Gabius, H.-J.: Introduction of extended LEC14-type branching into core-fucosylated biantennary N-glycan: glycoengineering for enhanced cell binding and serum clearance of the neoglycoprotein. FEBS J. 272, 1986–1998 (2005)

    Article  PubMed  Google Scholar 

  38. André, S., Kojima, S., Gundel, G., Russwurm, R., Schratt, X., Unverzagt, C., Gabius, H.-J.: Branching mode in complex-type triantennary N-glycans as regulatory element of their ligand properties. Biochim. Biophys. Acta 1760, 768–782 (2006)

    Article  PubMed  Google Scholar 

  39. André, S., Kožár, T., Schuberth, R., Unverzagt, C., Kojima, S., Gabius, H.-J.: Substitutions in the N-Glycan core as regulators of biorecognition: the case of core-fucose and bisecting GlcNAc moieties. Biochemistry 46, 6984–6995 (2007)

    Article  PubMed  Google Scholar 

  40. Gabius, H.-J., André, S., Jiménez-Barbero, J., Romero, A., Solís, D.: From lectin structure to functional glycomics: principles of the sugar code. Trends Biochem. Sci. 36, 298–313 (2011)

    Article  CAS  PubMed  Google Scholar 

  41. van Kasteren, S.I., Kramer, H.B., Jensen, H.H., Campbell, S.J., Kirkpatrick, J., Oldham, N.J., Anthony, D.C., Davis, B.G.: Expanding the diversity of chemical protein modification allows post-translational mimicry. Nature 446, 1105–1109 (2007)

    Article  PubMed  Google Scholar 

  42. Tanaka, K., Masuyama, T., Hasegawa, K., Tahara, T., Mizuma, H., Wada, Y., Watanabe, Y., Fukase, K.: A submicrogram-scale protocol for biomolecule-based PET imaging via rapid 6π-azaelectrocyclization: first visualization of sialic acid-dependent circulatory residence of glycoproteins. Angew. Chem. Int. Ed. 47, 102–105 (2008)

    Article  CAS  Google Scholar 

  43. Tanaka, K., Minami, K., Tahara, T., Fujii, Y., Siwu, E.R.O., Nozaki, S., Onoe, H., Yokoi, S., Koyama, K., Watanabe, Y., Fukase, K.: Electrocyclization-based labeling allows efficient in vivo imaging of cellular trafficking. ChemMedChem 5, 841–845 (2010)

    Article  CAS  PubMed  Google Scholar 

  44. Tanaka, K., Yokoi, S., Morimoto, K., Iwata, T., Nakamoto, Y., Nakayama, K., Koyama, K., Fujiwara, T., Fukase, K.: Cell surface biotinylation by azaelectrocyclization: easy-handling and versatile approach for living cell labeling. Bioorg. Med. Chem. 20, 1865–1868 (2012)

    Article  CAS  PubMed  Google Scholar 

  45. Tanaka, K., Moriwaki, K., Yokoi, S., Koyama, K., Miyoshi, E., Fukase, K.: Whole-body imaging of tumor cells by azaelectrocyclization: visualization of metastasis dependence on glycan structure. Bioorg. Med. Chem. 21, 1074–1077 (2013)

    Article  CAS  PubMed  Google Scholar 

  46. Tanaka, K., Nakamoto, Y., Siwu, E.R.O., Pradipta, A.R., Morimoto, K., Fujiwara, T., Yoshida, S., Hosoya, T., Tamura, Y., Hirai, G., Sodeoka, M., Fukase, K.: Development of bis-unsaturated ester aldehydes as amino-glue probes: sequential double azaelectrocyclization as promising strategy for bioconjugation. Org. Biomol. Chem. 11, 7326–7333 (2013)

    Article  CAS  PubMed  Google Scholar 

  47. Tanaka, K., Minami, K., Tahara, T., Siwu, E.R.O., Koyama, K., Nozaki, S., Onoe, H., Watanabe, Y., Fukase, K.: A combined 6π-azaelectrocyclization/Staudinger approach to protein & cell engineering: non-invasive tumor targeting by N-glycan-engineered lymphocytes. J. Carbohydr. Chem. 29, 118–132 (2010)

    Article  CAS  Google Scholar 

  48. Tanaka, K., Siwu, E.R.O., Minami, K., Hasegawa, K., Nozaki, S., Kanayama, Y., Koyama, K., Chen, W.C., Paulson, J.C., Watanabe, Y., Fukase, K.: Noninvasive imaging of dendrimer-type N-glycan clusters: in vivo dinamics dependence on oligosaccharides structure. Angew. Chem. Int. Ed. 49, 8195–8200 (2010)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, 22651081, 23681047, and 25560410, by a Research Grant from the Mizutani Foundation for Glycoscience, by a MEXT Grant-in-Aid for Scientific Research on Innovative Areas “Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity”, by an AstraZeneca R&D Grant, and by a subsidy of the Russian Government “Program of Competitive Growth of Kazan Federal University among World's Leading Academic Centers”.

Author information

Authors and Affiliations

  1. Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan

    Akihiro Ogura & Katsunori Tanaka

  2. Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya street, Kazan, 420008, Russia

    Almira Kurbangalieva

Authors
  1. Akihiro Ogura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Almira Kurbangalieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katsunori Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katsunori Tanaka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ogura, A., Kurbangalieva, A. & Tanaka, K. In vivo kinetics and biodistribution analysis of neoglycoproteins: effects of chemically introduced glycans on proteins. Glycoconj J 31, 273–279 (2014). https://doi.org/10.1007/s10719-014-9520-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-014-9520-3

Keywords

Search

Navigation