Design of an Automated Reagent-Dispensing System for Reaction Screening and Validation with DNA-Tagged Substrates

ACS Comb Sci. 2020 Mar 9;22(3):101-108. doi: 10.1021/acscombsci.9b00207. Epub 2020 Feb 27.

Abstract

Laboratory automation strategies have vast potential for accelerating discovery processes. They enable higher efficiency and throughput for time-consuming screening procedures and reduce error-prone manual steps. Automating repetitive procedures can for instance support chemists in optimizing chemical reactions. Particularly, the technology of DNA-encoded libraries (DELs) may benefit from automation techniques, since translation of chemical reactions to DNA-tagged reactants often requires screening of multiple reaction parameters and evaluation of large numbers of reactants. Here, we describe a portable, automated system for reagent dispensing that was designed from open source materials. The system was validated by performing amide coupling of carboxylic acids to DNA-linked amine and a micelle-mediated Povarov reaction to DNA-tagged hexahydropyrroloquinolines. The latter reaction required accurate pipetting of multiple components including different solvents and a surface-active reagent. Analysis of reactions demonstrated that the robotic system achieved high accuracy comparable to experimentation by an experienced chemist with the potential of higher throughput.

Keywords: DNA-encoded chemistry; automated reagent dispensing; laboratory automation; micellar catalysis; robot.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Amines / chemistry*
  • Automation
  • Carboxylic Acids / chemistry*
  • Combinatorial Chemistry Techniques*
  • DNA / chemistry*
  • Drug Design
  • Drug Evaluation, Preclinical
  • Molecular Structure
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry

Substances

  • Amides
  • Amines
  • Carboxylic Acids
  • Pyrroles
  • Quinolines
  • pyrroloquinoline
  • DNA