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Avidity mechanism of dendrimer-folic acid conjugates.

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.

SUBMITTER: van Dongen MA

PROVIDER: S-EPMC4018099 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Avidity mechanism of dendrimer-folic acid conjugates.

van Dongen Mallory A MA Silpe Justin E JE Dougherty Casey A CA Kanduluru Ananda Kumar AK Choi Seok Ki SK Orr Bradford G BG Low Philip S PS Banaszak Holl Mark M MM

Molecular pharmaceutics 20140411 5

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 sy ...[more]

PMID: 24725205

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