Avidity mechanism of dendrimer-folic acid conjugates.
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.
Department of Chemistry and ⊥Department of Physics, ‡Program in Macromolecular Sciences and Engineering, and §Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan , Ann Arbor, Michigan 48019, United States.
Mallory A
MA
van Dongen
Justin E
JE
Silpe
Casey A
CA
Dougherty
Ananda Kumar
AK
Kanduluru
Seok Ki
SK
Choi
Bradford G
BG
Orr
Philip S
PS
Low
Mark M
MM
Banaszak Holl
D002352:Carrier Proteins; D050091:Dendrimers / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry*; D008962:Models, Theoretical; D011485:Protein Binding
D002352:Carrier Proteins; D050091:Dendrimers; C104700:PAMAM Starburst; D005492:Folic Acid