Avidity mechanism of dendrimer-folic acid conjugates

Mallory A. van Dongen, Justin E. Silpe, Casey A. Dougherty, Ananda Kumar Kanduluru, Seok Ki Choi, Bradford G. Orr, Philip S. Low, Mark M. Banaszak Holl

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Multivalent conjugation of folic acid has been employed to target cells overexpressing folate receptors. Such polymer conjugates have been previously demonstrated to have high avidity to folate binding protein. However, the lack of a monovalent folic acid-polymer material has prevented a full binding analysis of these conjugates, as multivalent binding mechanisms and polymer-mass mechanisms are convoluted in samples with broad distributions of folic acid-to-dendrimer ratios. In this work, the synthesis of a monovalent folic acid-dendrimer conjugate allowed the elucidation of the mechanism for increased binding between the folic acid-polymer conjugate and a folate binding protein surface. The increased avidity is due to a folate-keyed interaction between the dendrimer and protein surfaces that fits into the general framework of slow-onset, tight-binding mechanisms of ligand/protein interactions.

Original languageEnglish
Pages (from-to)1696-1706
Number of pages11
JournalMolecular Pharmaceutics
Volume11
Issue number5
DOIs
Publication statusPublished - 5 May 2014
Externally publishedYes

Keywords

  • folic acid
  • multivalent binding
  • PAMAM dendrimer
  • polymer/protein interactions

Cite this

van Dongen, M. A., Silpe, J. E., Dougherty, C. A., Kanduluru, A. K., Choi, S. K., Orr, B. G., ... Banaszak Holl, M. M. (2014). Avidity mechanism of dendrimer-folic acid conjugates. Molecular Pharmaceutics, 11(5), 1696-1706. https://doi.org/10.1021/mp5000967
van Dongen, Mallory A. ; Silpe, Justin E. ; Dougherty, Casey A. ; Kanduluru, Ananda Kumar ; Choi, Seok Ki ; Orr, Bradford G. ; Low, Philip S. ; Banaszak Holl, Mark M. / Avidity mechanism of dendrimer-folic acid conjugates. In: Molecular Pharmaceutics. 2014 ; Vol. 11, No. 5. pp. 1696-1706.
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van Dongen, MA, Silpe, JE, Dougherty, CA, Kanduluru, AK, Choi, SK, Orr, BG, Low, PS & Banaszak Holl, MM 2014, 'Avidity mechanism of dendrimer-folic acid conjugates' Molecular Pharmaceutics, vol. 11, no. 5, pp. 1696-1706. https://doi.org/10.1021/mp5000967

Avidity mechanism of dendrimer-folic acid conjugates. / van Dongen, Mallory A.; Silpe, Justin E.; Dougherty, Casey A.; Kanduluru, Ananda Kumar; Choi, Seok Ki; Orr, Bradford G.; Low, Philip S.; Banaszak Holl, Mark M.

In: Molecular Pharmaceutics, Vol. 11, No. 5, 05.05.2014, p. 1696-1706.

Research output: Contribution to journalArticleResearchpeer-review

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AU - van Dongen, Mallory A.

AU - Silpe, Justin E.

AU - Dougherty, Casey A.

AU - Kanduluru, Ananda Kumar

AU - Choi, Seok Ki

AU - Orr, Bradford G.

AU - Low, Philip S.

AU - Banaszak Holl, Mark M.

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van Dongen MA, Silpe JE, Dougherty CA, Kanduluru AK, Choi SK, Orr BG et al. Avidity mechanism of dendrimer-folic acid conjugates. Molecular Pharmaceutics. 2014 May 5;11(5):1696-1706. https://doi.org/10.1021/mp5000967