title: Biophysical characterization of a riboflavin-conjugated dendrimer platform for targeted drug delivery.
abstract: The present study describes the biophysical characterization of generation-five poly(amidoamine) (PAMAM) dendrimers conjugated with riboflavin (RF) as a cancer-targeting platform. Two new series of dendrimers were designed, each presenting the riboflavin ligand attached at a different site (isoalloxazine at N-3 and d-ribose at N-10) and at varying ligand valency. Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) were used to determine the binding activity for riboflavin binding protein (RfBP) in a cell-free solution. The ITC data shows dendrimer conjugates have K(D) values of ≥ 465 nM on a riboflavin basis, an affinity ~93-fold lower than that of free riboflavin. The N-3 series showed greater binding affinity in comparison with the N-10 series. Notably, the affinity is inversely correlated with ligand valency. These findings are also corroborated by DSC, where greater protein-conjugate stability is achieved with the N-3 series and at lower ligand valency.
authors.affiliation: Department of Chemistry & Biochemistry, Calvin College, 3201 Burton Street South East, Grand Rapids, Michigan 49546, United States.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Witte
authors.forename: Christine M
authors.initials: CM
authors.lastname: Timmer
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Gam
authors.forename: Seok Ki
authors.initials: SK
authors.lastname: Choi
authors.forename: Mark M
authors.initials: MM
authors.lastname: Banaszak Holl
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Orr
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.forename: Kumar
authors.initials: K
authors.lastname: Sinniah
mesh_terms: D002152:Calorimetry, Differential Scanning; D016503:Drug Delivery Systems; D005415:Flavins / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D012256:Riboflavin / Q000737:chemistry*; D012266:Ribose / Q000737:chemistry*; D012996:Solutions; D013816:Thermodynamics
chemical_list: D005415:Flavins; D008024:Ligands; D012996:Solutions; C008173:isoalloxazine; D012266:Ribose; D012256:Riboflavin