title: Label-Free Real-Time Microarray Imaging of Cancer Protein-Protein Interactions and Their Inhibition by Small Molecules.
abstract: A rapid optical microarray imaging approach for anticancer drug screening at specific cancer protein-protein interface targets with binding kinetics and validation by a mass sensor is reported for the first time. Surface plasmon resonance imager (SPRi) demonstrated a 3.5-fold greater specificity for interactions between murine double minute 2 protein (MDM2) and wild-type p53 over a nonspecific p53 mutant in a real-time microfluidic analysis. Significant percentage reflectivity changes (Δ%R) in the SPRi signals and molecular-level mass changes were detected for both the MDM2-p53 interaction and its inhibition by a small-molecule Nutlin-3 drug analogue known for its anticancer property. We additionally demonstrate that synthetic, inexpensive binding domains of interacting cancer proteins are sufficient to screen anticancer drugs by an array-based SPRi technique with excellent specificity and sensitivity. This imaging array, combined with a mass sensor, can be used to study quantitatively any protein-protein interaction and screen for small molecules with binding and potency evaluations.
authors.forename: Charuksha
authors.initials: C
authors.lastname: Walgama
authors.forename: Zainab H
authors.initials: ZH
authors.lastname: Al Mubarak
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Mayowa
authors.initials: M
authors.lastname: Akinwale
authors.forename: Anuruddha
authors.initials: A
authors.lastname: Pathiranage
authors.forename: Junpeng
authors.initials: J
authors.lastname: Deng
authors.forename: K Darrell
authors.initials: KD
authors.lastname: Berlin
authors.affiliation: Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73104, United States.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Benbrook
authors.forename: Sadagopan
authors.initials: S
authors.lastname: Krishnan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011789:Quantum Theory; D046888:Tissue Array Analysis
chemical_list: D009363:Neoplasm Proteins