Restored physiology in protein-deficient yeast by a small molecule channel

Alexander G. Cioffi, Jennifer Hou, Anthony S. Grillo, Katrina A. Diaz, Martin D. Burke

Research output: Contribution to journalArticlepeer-review

Abstract

Deficiencies of protein ion channels underlie many currently incurable human diseases. Robust networks of pumps and channels are usually responsible for the directional movement of specific ions in organisms ranging from microbes to humans. We thus questioned whether minimally selective small molecule mimics of missing protein channels might be capable of collaborating with the corresponding protein ion pumps to restore physiology. Here we report vigorous and sustainable restoration of yeast cell growth by replacing missing protein ion transporters with imperfect small molecule mimics. We further provide evidence that this tolerance for imperfect mimicry is attributable to collaboration between the channel-forming small molecule and protein ion pumps. These results illuminate a mechanistic framework for pursuing small molecule replacements for deficient protein ion channels that underlie a range of challenging human diseases.

Original languageEnglish (US)
Pages (from-to)10096-10099
Number of pages4
JournalJournal of the American Chemical Society
Volume137
Issue number32
DOIs
StatePublished - Aug 19 2015

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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