Plasmonic ruler on field-effect devices for kinase drug discovery applications

Nikhil Bhalla, Nello Formisano, Anna Miodek, Aditya Jain, Mirella Di Lorenzo, Giordano Pula, Pedro Estrela

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Protein kinases are cellular switches that mediate phosphorylation of proteins. Abnormal phosphorylation of proteins is associated with lethal diseases such as cancer. In the pharmaceutical industry, protein kinases have become an important class of drug targets. This study reports a versatile approach for the detection of protein phosphorylation. The change in charge of the myelin basic protein upon phosphorylation by the protein kinase C-alpha (PKC-α) in the presence of adenosine 5'-[γ-thio] triphosphate (ATP-S) was detected on gold metal-insulator-semiconductor (Au-MIS) capacitor structures. Gold nanoparticles (AuNPs) can then be attached to the thio-phosphorylated proteins, forming a Au-film/AuNP plasmonic couple. This was detected by a localized surface plasmon resonance (LSPR) technique alongside MIS capacitance. All reactions were validated using surface plasmon resonance technique and the interaction of AuNPs with the thio-phosphorylated proteins quantified by quartz crystal microbalance. The plasmonic coupling was also visualized by simulations using finite element analysis. The use of this approach in drug discovery applications was demonstrated by evaluating the response in the presence of a known inhibitor of PKC-α kinase. LSPR and MIS on a single platform act as a cross check mechanism for validating kinase activity and make the system robust to test novel inhibitors.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalBiosensors and Bioelectronics
Volume71
Early online date8 Apr 2015
DOIs
Publication statusPublished - 15 Sep 2015

Keywords

  • Drug discovery
  • Localized surface plasmon resonance
  • Metal-insulator-semiconductor
  • Nanoplasmonics
  • Protein phosphorylation

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