title: Bioanalytical Screening of Riboflavin Antagonists for Targeted Drug Delivery - A Thermodynamic and Kinetic Study.
abstract: The present study screened riboflavin mimicking small molecules to determine their binding activity for the riboflavin binding protein. We performed thermodynamic and kinetic binding studies of these molecules using a combination of two analytical approaches; isothermal titration calorimetry and surface plasmon resonance spectroscopy. Screening of a biased set of non-riboflavin based small molecules by microcalorimetry led to the discovery of two known drug molecules, quinacrine and chloroquine, as favorable ligands for the riboflavin receptor with K(D) value of 264, and 2100 nM, respectively. We further demonstrated that quinacrine is a competitive ligand for the receptor as measured by surface plasmon resonance. Thus this study describes the identification of a novel class of dual acting riboflavin antagonists that target riboflavin receptor for cellular uptake and display multifunctional activities upon cellular entry.
authors.affiliation: Calvin College, Department of Chemistry & Biochemistry, 3201 Burton St. SE Grand Rapids, MI 49546.
authors.forename: Anna
authors.initials: A
authors.lastname: Plantinga
authors.forename: Amanda
authors.initials: A
authors.lastname: Witte
authors.forename: Ming-Hsin
authors.initials: MH
authors.lastname: Li
authors.forename: Andrew
authors.initials: A
authors.lastname: Harmon
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