Firefly luciferase inhibitor-conjugated peptide quenches bioluminescence: a versatile tool for real time monitoring cellular uptake of biomolecules

Bioconjug Chem. 2014 Jan 15;25(1):4-10. doi: 10.1021/bc4003713. Epub 2013 Dec 19.

Abstract

In this paper, novel firefly luciferase-specific inhibitor compounds (FLICs) are evaluated as potential tools for cellular trafficking of transporter conjugates. As a proof-of-concept, we designed FLICs that were suitable for solid phase peptide synthesis and could be covalently conjugated to peptides via an amide bond. The spacer between inhibitor and peptide was optimized to gain efficient inhibition of recombinant firefly luciferase (FLuc) without compromising the activity of the model peptides. The hypothesis of using FLICs as tools for cellular trafficking studies was ensured with U87Fluc glioblastoma cells expressing firefly luciferase. Results show that cell penetrating peptide (penetratin) FLIC conjugate 9 inhibited FLuc penetrated cells efficiently (IC50 = 1.6 μM) and inhibited bioluminescence, without affecting the viability of the cells. Based on these results, peptide-FLIC conjugates can be used for the analysis of cellular uptake of biomolecules in a new way that can at the same time overcome some downsides seen with other methods. Thus, FLICs can be considered as versatile tools that broaden the plethora of methods that take advantage of the bioluminescence phenomena.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Cell-Penetrating Peptides
  • Dose-Response Relationship, Drug
  • Fireflies / enzymology*
  • Humans
  • Isoxazoles / chemistry*
  • Isoxazoles / pharmacokinetics
  • Isoxazoles / pharmacology*
  • Kinetics
  • Luciferases, Firefly / antagonists & inhibitors
  • Luciferases, Firefly / metabolism
  • Luminescence*
  • Luminescent Measurements
  • Molecular Structure
  • Structure-Activity Relationship
  • Time Factors
  • Tissue Distribution

Substances

  • Carrier Proteins
  • Cell-Penetrating Peptides
  • Isoxazoles
  • penetratin
  • Luciferases, Firefly