Identification of toxin inhibitors using a magnetic nanosensor-based assay

Small
Oscar J SantiestebanJ Manuel Perez

Abstract

A magnetic nanosensor-based method is described to screen a library of drugs for potential binding to toxins. Screening is performed by measuring changes in the magnetic relaxation signal of the nanosensors (bMR nanosensors) in aqueous suspension upon addition of the toxin. The Anthrax lethal factor (ALF) is selected as a model toxin to test the ability of our bMR nanosensor-based screening method to identify potential inhibitors of the toxin. Out of 30 molecules screened, sulindac, naproxen and fusaric acid are found to bind LF, with dissociation constants in the low micromolar range. Further biological analysis of the free molecules in solution indicate that sulindac and its metabolic products inhibited LF cytotoxicity to macrophages with IC50 values in the micromolar range. Meanwhile, fusaric acid is found to be less effective at inhibiting LF cytotoxicity, while naproxen does not inhibit LF toxicity. Most importantly, when the sulindac and fusaric acid-bMR nanosensors themselves are tested as LF inhibitors, as opposed to the corresponding free molecules, they are stronger inhibitors of LF with IC50 values in the nanomolar range. Taken together, these studies show that a bMR nanosensors-based assay can be used to screen know...Continue Reading

References

Nov 9, 2001·Nature·A D PanniferR C Liddington
Dec 19, 2001·Emerging Infectious Diseases·J A JerniganUNKNOWN Anthrax Bioterrorism Investigation Team
Jul 26, 2002·Nature·Fiorella TonelloCesare Montecucco
Jan 25, 2003·Cellular Microbiology·Michèle Mock, Tâm Mignot
Jan 14, 2004·Nature Structural & Molecular Biology·Rekha G PanchalSina Bavari
Jun 29, 2005·Proceedings of the National Academy of Sciences of the United States of America·Martino ForinoMaurizio Pellecchia
Feb 15, 2007·Nano Letters·Charalambos KaittanisJ Manuel Perez
Mar 20, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Joel M ReidUNKNOWN Cancer Prevention Network
May 14, 2008·Journal of the American Chemical Society·Mary-Catherine BowmanChristian Melander
Sep 25, 2008·Neoplasia : an International Journal for Oncology Research·J Manuel PerezRalph Weissleder
Apr 11, 2009·Bioorganic & Medicinal Chemistry·Sherida L JohnsonMaurizio Pellecchia
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Jul 1, 2009·Molecular Aspects of Medicine·R John Collier
Jul 30, 2009·Molecular Aspects of Medicine·Mahtab Moayeri, Stephen H Leppla
Feb 24, 2011·Journal of the American Chemical Society·Charalambos KaittanisJ Manuel Perez
Feb 25, 2011·Science Translational Medicine·Jered B HaunRalph Weissleder
Nov 19, 2011·Protein Science : a Publication of the Protein Society·James G Bann
May 9, 2012·Microbial Pathogenesis·Hae-Chul ParkMoon-Young Yoon
May 26, 2012·Angewandte Chemie·Oscar J SantiestebanJ Manuel Perez

❮ Previous
Next ❯

Citations

Jun 9, 2016·Sensors·Stefan SchrittwieserJoerg Schotter

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthrax Vaccines

Three different types of anthrax vaccines are available; a live-attenuated, an alum-precipitated cell-free filtrate and a protein recombinant vaccine. The effectiveness between the three is uncertain, but the live-attenuated have shown to reduce the risk of anthrax with low adverse events. Here is the latest research on anthrax vaccines.

Anthrax

Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Here is the latest research on Anthrax.

Anthrax Vaccines (ASM)

Three different types of anthrax vaccines are available; a live-attenuated, an alum-precipitated cell-free filtrate and a protein recombinant vaccine. The effectiveness between the three is uncertain, but the live-attenuated have shown to reduce the risk of anthrax with low adverse events. Here is the latest research on anthrax vaccines.