1 research outputs found
Label-Free Real-Time Microarray Imaging of Cancer Protein–Protein Interactions and Their Inhibition by Small Molecules
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%<i>R</i>) 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