Tim MacKenzie

All Publications

• A Primer on the Stanford Budget or: How I Learned to Stop Worrying and Love the Endowment MacKenzie, T. M. The Stanford Daily. https://stanforddaily.com/2022/04/13/from-the-community-a-primer-on-the-stanford-budget/. 2022
• Student Activism, not Endowment Returns, Led to Recent Affordability Initiatives MacKenzie, T. M. The Stanford Daily. https://stanforddaily.com/2022/02/02/from-the-community-student-activism-not-endowment-returns-led-to-recent-affordability-initiatives/. 2022
• Differential effects of modified batrachotoxins on voltage-gated sodium channel fast and slow inactivation. Cell chemical biology MacKenzie, T. M., Abderemane-Ali, F., Garrison, C. E., Minor, D. L., Bois, J. D. 2021

  Abstract

  Voltage-gated sodium channels (NaVs) are targets for a number of acute poisons. Many of these agents act as allosteric modulators of channel activity and serve as powerful chemical tools for understanding channel function. Herein, we detail studies with batrachotoxin (BTX), a potent steroidal amine, and three ester derivatives prepared through de novo synthesis against recombinant NaV subtypes (rNaV1.4 and hNaV1.5). Two of these compounds, BTX-B and BTX-cHx, are functionally equivalent to BTX, hyperpolarizing channel activation and blocking both fast and slow inactivation. BTX-yne-a C20-n-heptynoate ester-is a conspicuous outlier, eliminating fast but not slow inactivation. This property differentiates BTX-yne among other NaV modulators as a unique reagent that separates inactivation processes. These findings are supported by functional studies with bacterial NaVs (BacNaVs) that lack a fast inactivation gate. The availability of BTX-yne should advance future efforts aimed at understanding NaV gating mechanisms and designing allosteric regulators of NaV activity.

  View details for DOI 10.1016/j.chembiol.2021.12.003

  View details for PubMedID 34963066