Publication

A Screening Platform to Identify and Tailor Biocompatible Small-Molecule Catalysts

Rubini, R., Ivanov, I. & Mayer, C., 13-Dec-2019, In : Chemistry. 25, 70, p. 16017-16021 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)16017-16021
Number of pages6
JournalChemistry
Volume25
Issue number70
Publication statusPublished - 13-Dec-2019

    Keywords

  • biocompatible catalysis, catalyst screening, metabolism, non-canonical amino acids, uncaging, BIOORTHOGONAL CATALYSIS, TRANSFER HYDROGENATION, DIRECTED EVOLUTION, CHEMISTRY, CLEAVAGE, ACTIVATION, COMPLEX, SYSTEM

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