A Screening Platform to Identify and Tailor Biocompatible Small‐Molecule Catalysts. Issue 70 (18th November 2019)

• Record Type: Journal Article
• Authors: Rubini, Rudy; Ivanov, Ilya; Mayer, Clemens
• Is Part Of: Chemistry. Volume 25:Issue 70(2019)
• Page Start: 16017
• Page End: 16021
• Publication Date: 2019-11-18
• Subjects: biocompatible catalysis -- catalyst screening -- metabolism -- non-canonical amino acids -- uncaging; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201904808
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Interfacing biocompatible, small‐molecule catalysis with cellular metabolism promises a straightforward introduction of new function into organisms without the need for genetic manipulation. However, identifying and optimizing synthetic catalysts that perform new‐to‐nature transformations under conditions that support life is a cumbersome task. To enable the rapid discovery and fine‐tuning of biocompatible catalysts, we describe a 96‐well screening platform that couples the activity of synthetic catalysts to yield non‐canonical amino acids from appropriate precursors with the subsequent incorporation of these nonstandard building blocks into GFP (quantifiable readout). Critically, this strategy does not only provide a common readout (fluorescence) for different reaction/catalyst combinations, but also informs on the organism's fitness, as stop codon suppression relies on all steps of the central dogma of molecular biology. To showcase our approach, we have applied it to the evaluation and optimization of transition‐metal‐catalyzed deprotection reactions. Abstract : A multi‐well screen that rapidly reports the catalytic activity of transition‐metal catalysts in presence of live cells is reported. The activity of a catalyst to yield a non‐canonical amino acid (ncAA) from an appropriate precursor is coupled to the incorporation of the nonstandard building block into GFP (quantifiable readout; see scheme).