Biophysical characterization of a riboflavin-conjugated dendrimer platform for targeted drug delivery |
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Authors: | Witte Amanda B Timmer Christine M Gam Jeremy J Choi Seok Ki Banaszak Holl Mark M Orr Bradford G Baker James R Sinniah Kumar |
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Affiliation: | Department of Chemistry & Biochemistry, Calvin College, 3201 Burton Street South East, Grand Rapids, Michigan 49546, United States. |
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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. |
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