Document Type

Article

Publication Title

ACS Medicinal Chemistry Letters

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 nonriboflavin-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 KD values 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. © 2011 American Chemical Society.

First Page

363

Last Page

367

DOI

10.1021/ml100296z

Publication Date

5-12-2011

Included in

Chemistry Commons

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