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The synthesis of TNF-alpha conjugates with alendronic acid

Abstract

Conjugates of recombinant human tumor necrosis factor alpha (TNFα) and alendronic acid linked through the protein sulfhydryl, carboxyl, and amino groups were obtained with crosslinking agents of different types. The conjugation reactions were conducted in solution and on a solid phase. Unlike the conjugation reactions in solution, the method involving immobilization of active components on a hydroxyapatite column was shown to result in the conjugates with a specified stoichiometry and a high degree of homogeneity. The TNFα conjugates retained the specific cytolytic activity and demonstrated the higher affinity to hydroxyapatite, an analogue of the bone mineral matrix, than TNFα.

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Abbreviations

ALN:

alendronic acid

EDC:

1-ethyl-3-[3-dimethylaminopropyl]carbodiimide

GLT:

glutaric aldehyde

HAP:

hydroxyapatite

Sulfo-SMCC:

sulfosuccinimidyl-4-(Nmaleimidomethyl) cyclohexane-1-carboxylate

TNFα:

tumor necrosis factor

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Correspondence to E. A. Volosnikova.

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Original Russian Text © E.A. Volosnikova, I.F. Demin, G.M. Levagina, L.R. Lebedev, A.I. Zakabunin, E.D. Danilenko, 2016, published in Bioorganicheskaya Khimiya, 2016, Vol. 42, No. 6, pp. 704–711.

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Volosnikova, E.A., Demin, I.F., Levagina, G.M. et al. The synthesis of TNF-alpha conjugates with alendronic acid. Russ J Bioorg Chem 42, 638–645 (2016). https://doi.org/10.1134/S1068162016060145

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  • DOI: https://doi.org/10.1134/S1068162016060145

Keywords

  • alendronic acid
  • binding to hydroxyapatite
  • conjugation
  • tumor necrosis factor alpha recombinant human