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Related Experiment Videos

Two-dimensional parallel array technology as a new approach to automated combinatorial solid-phase organic synthesis

Brennan1, Biddison, Frauendorf

  • 1ProtoGene Laboratories, 1454 Page Mill Road, Palo Alto, California 94304, USA.

Biotechnology and Bioengineering
|April 1, 1999
PubMed
Summary

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A new automated synthesizer enables rapid parallel synthesis of numerous compounds using a unique reagent delivery system. This high-throughput method efficiently produces diverse chemical libraries for drug discovery screening.

Area of Science:

  • Organic Chemistry
  • Chemical Engineering
  • Drug Discovery

Background:

  • Solid-phase organic synthesis (SPOS) is crucial for combinatorial chemistry.
  • Existing methods for parallel synthesis can be time-consuming and labor-intensive.
  • Need for automated, high-throughput synthesis platforms to accelerate lead discovery.

Purpose of the Study:

  • To design and construct an automated 96-well parallel array synthesizer for SPOS.
  • To develop a novel reagent array delivery system for efficient compound synthesis.
  • To demonstrate the utility of the synthesizer in preparing a combinatorial library for biological screening.

Main Methods:

  • The instrument features a unique reagent array delivery format with dedicated plumbing for each reagent.

Related Experiment Videos

  • An inert atmosphere and controlled temperature are maintained throughout the synthesis process.
  • Automated software controls reagent delivery to 96 wells via X-Y axis movement of reaction plates and nozzle blocks.

    • Main Results:

    • The parallel array synthesizer successfully prepared approximately 1300 hydroxamic acid compounds in a few weeks.
    • The synthesized crude compounds exhibited high purity (>80%) suitable for direct use in high-throughput screening.
    • Several active compounds were identified in antibacterial assays, validating the system's efficiency.

    Conclusions:

    • The developed automated synthesizer is an efficient platform for parallel synthesis.
    • The system facilitates rapid generation of compound libraries for lead discovery.
    • This technology accelerates the identification of biologically active molecules.