Specificity and Speed: Tethered Photopharmacology

Philipp Leippe, Julia Koehler Leman, Dirk Trauner

Research output: Contribution to journalReview articlepeer-review


Genetics and pharmacology are often seen as two distinct approaches to interrogating, elucidating, and manipulating biological systems. The former is renowned for its precision whereas the latter for its fast kinetics, reversibility, and practicality. Here, we show that both can be joined as "tethered pharmacology", wherein a genetically programmed bioconjugation site provides selectivity and a tethered pharmacophore provides function. The speed of onset, and especially cessation, of pharmacological activity can be greatly enhanced by incorporating photoswitches and using light as the trigger ("tethered photopharmacology"). Genetically encoded, tethered photopharmacology is a variant of optogenetics and could even play a role in medicine wherever gene therapy is viable. However, gene therapy may not be necessary if sufficiently selective tethering strategies that operate on wild-type receptors can be developed.

Original languageEnglish (US)
Pages (from-to)5214-5220
Number of pages7
Issue number39
StatePublished - Oct 3 2017

ASJC Scopus subject areas

  • Biochemistry


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