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 journalArticle

44 Scopus citations

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 (US)
Pages (from-to)1696-1706
Number of pages11
JournalMolecular pharmaceutics
Volume11
Issue number5
DOIs
StatePublished - May 5 2014

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Pharmaceutical Science

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