Fluorescence activation mechanism and imaging of drug permeation with new sensors for smoking-cessation ligands

  1. Aaron L Nichols
  2. Zack Blumenfeld
  3. Chengcheng Fan
  4. Laura Luebbert
  5. Annet EM Blom
  6. Bruce N Cohen
  7. Jonathan S Marvin
  8. Philip M Borden
  9. Charlene H Kim
  10. Anand K Muthusamy
  11. Amol V Shivange
  12. Hailey J Knox
  13. Hugo Rego Campello
  14. Jonathan H Wang
  15. Dennis A Dougherty
  16. Loren L Looger
  17. Timothy Gallagher
  18. Douglas C Rees
  19. Henry A Lester  Is a corresponding author
  1. Division of Biology and Biological Engineering, California Institute of Technology, United States
  2. Keck School of Medicine, University of Southern California, United States
  3. Division of Chemistry and Chemical Engineering, California Institute of Technology, United States
  4. Institute of Biology, Leiden University, Netherlands
  5. Janelia Research Campus, Howard Hughes Medical Institute, United States
  6. School of Chemistry, University of Bristol, United Kingdom
  7. Howard Hughes Medical Institute, California Institute of Technology, United States

Peer review process

This article was accepted for publication as part of eLife's original publishing model.

History

  1. Version of Record updated
  2. Version of Record updated
  3. Version of Record published
  4. Accepted Manuscript published
  5. Accepted
  6. Received
  7. Preprint posted

Decision letter

  1. Gary Yellen
    Reviewing Editor; Harvard Medical School, United States
  2. Kenton J Swartz
    Senior Editor; National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
  3. Ryan E Hibbs
    Reviewer; University of Texas Southwestern Medical Center, United States
  4. Thomas E Hughes
    Reviewer; Montana State University, United States
  5. Owen McManus
    Reviewer

Our editorial process produces two outputs: (i) public reviews designed to be posted alongside the preprint for the benefit of readers; (ii) feedback on the manuscript for the authors, including requests for revisions, shown below. We also include an acceptance summary that explains what the editors found interesting or important about the work.

Decision letter after peer review:

Thank you for submitting your article "Fluorescence Activation Mechanism and Imaging of Drug Permeation with New Sensors for Smoking-Cessation Ligands" for consideration by eLife. Your article has been reviewed by 3 peer reviewers, and the evaluation has been overseen by a Reviewing Editor and Kenton Swartz as the Senior Editor. The following individuals involved in review of your submission have agreed to reveal their identity: Ryan E Hibbs (Reviewer #1); Thomas E. Hughes (Reviewer #2); Owen McManus (Reviewer #3).

The reviewers have discussed their reviews with one another, and the Reviewing Editor has drafted this to help you prepare a revised submission.

Congratulations on an excellent piece of work!

Essential revisions:

Please make changes to the text for clarity and answer the individual small questions raised in the reviewers' recommendations below. Also, several reviewers agreed that the impact and interest of the paper for the audience could be broadened by adding a little material to the discussion about how analogous tools may be useful beyond the explicit case of nicotine addiction.

Reviewer #2 (Recommendations for the authors):

Great read, this is a beautiful piece of work. My only concern is that the paper covers such a broad swath of disciplines that it might be better with additional background? Biosensor people know remarkably little about target engagement issues in drug discover, pharmacologists are only vaguely aware of biosensors, and medicinal chemists are on a different planet. Is there a way to frame the bigger picture beyond nicotine addiction? It's so easy to see how this sort of approach could be used in SAR in different drug discovery campaigns for example.

https://doi.org/10.7554/eLife.74648.sa1

Author response

Essential revisions:

Please make changes to the text for clarity and answer the individual small questions raised in the reviewers' recommendations below. Also, several reviewers agreed that the impact and interest of the paper for the audience could be broadened by adding a little material to the discussion about how analogous tools may be useful beyond the explicit case of nicotine addiction.

The revised Discussion adds the explicit statement:

“The iDrugSnFR paradigm will be useful beyond the explicit case of nicotine addiction, with application to other exogenous neural drugs.”

Reviewer #2 (Recommendations for the authors):

Great read, this is a beautiful piece of work. My only concern is that the paper covers such a broad swath of disciplines that it might be better with additional background? Biosensor people know remarkably little about target engagement issues in drug discover, pharmacologists are only vaguely aware of biosensors, and medicinal chemists are on a different planet. Is there a way to frame the bigger picture beyond nicotine addiction? It's so easy to see how this sort of approach could be used in SAR in different drug discovery campaigns for example.

Amusingly, none of the authors have ever taken a formal course in the disciplines noted: biosensors, drug discovery, pharmacology, medicinal chemistry, or (not mentioned) pharmacokinetics. Lightheartedly, we note that none of us are known to suffer from imposter syndrome.

More seriously, we have presented 2021 SfN abstracts on related biosensors for opioids, SSRIs, and rapidly acting antidepressants. When those papers are submitted and published, we hope to verify Reviewer 2’s prediction. Meanwhile, the revised Discussion ends with the Editor’s suggested statement:

“The iDrugSnFR paradigm will be useful beyond the explicit case of nicotine addiction, with application to other exogenous neural drugs.”

https://doi.org/10.7554/eLife.74648.sa2

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Aaron L Nichols
  2. Zack Blumenfeld
  3. Chengcheng Fan
  4. Laura Luebbert
  5. Annet EM Blom
  6. Bruce N Cohen
  7. Jonathan S Marvin
  8. Philip M Borden
  9. Charlene H Kim
  10. Anand K Muthusamy
  11. Amol V Shivange
  12. Hailey J Knox
  13. Hugo Rego Campello
  14. Jonathan H Wang
  15. Dennis A Dougherty
  16. Loren L Looger
  17. Timothy Gallagher
  18. Douglas C Rees
  19. Henry A Lester
(2022)
Fluorescence activation mechanism and imaging of drug permeation with new sensors for smoking-cessation ligands
eLife 11:e74648.
https://doi.org/10.7554/eLife.74648

Share this article

https://doi.org/10.7554/eLife.74648