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A fully automated flow-based approach for accelerated peptide synthesis

Nature Chemical Biology volume 13, pages 464466 (2017) | Download Citation

Abstract

Here we report a fully automated, flow-based approach to solid-phase polypeptide synthesis, with amide bond formation in 7 seconds and total synthesis times of 40 seconds per amino acid residue. Crude peptide purities and isolated yields were comparable to those for standard-batch solid-phase peptide synthesis. At full capacity, this approach can yield tens of thousands of individual 30-mer peptides per year.

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Acknowledgements

This research was supported by startup funds from the MIT Department of Chemistry for B.L.P., the MIT Deshpande Center for Technological Innovation, and Dr. Reddy's Laboratories Limited and a National Science Foundation Graduate Student Fellowship for A.M. We also thank A. Teixeria, E. Evans, G. Lautrette, J. Wolfe, S. Jain, S. Kim, and A.J. West for expert technical assistance, suggestions, and as early adopters of the technology.

Author information

Author notes

    • Alexander J Mijalis
    •  & Dale A Thomas III

    These authors contributed equally to this work.

Affiliations

  1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Alexander J Mijalis
    • , Mark D Simon
    •  & Bradley L Pentelute
  2. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Dale A Thomas III
    • , Andrea Adamo
    •  & Klavs F Jensen
  3. R.M. Beaumont Corporation, Brunswick, Maine, USA.

    • Ryan Beaumont

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Contributions

D.A.T. and A.J.M. designed, coded, and assembled the AFPS and designed experiments to characterize it. R.B., A.J.M., and D.A.T. designed and implemented the LabView graphical interface and revised control electronics. M.D.S., A.J.M., D.A.T., and A.A. designed the valving and earlier prototype versions of the AFPS. A.J.M., D.A.T., M.D.S., K.F.J., and B.L.P. wrote the manuscript. K.F.J. and B.L.P. supervised the work.

Competing interests

Multiple patent applications covering this work have been filed by the MIT Technology Licensing Office. B.L.P. plans to commercialize this technology via a startup and will hold equity in the company.

Corresponding author

Correspondence to Bradley L Pentelute.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Results, Supplementary Tables 1–2 and Supplementary Figures 1–19

Videos

  1. 1.

    The movie shows a broad overview of the different components of the AFPS followed by its use in a typical synthesis.

    First, the user inputs a peptide sequence with all of the synthesis parameters. After pressing "run", the machine swells a syringe filled with resin with DMF and loads it into the heated reactor. During synthesis, the display shows UV, pressure, and temperature data. When the peptide synthesis is complete, the machine ejects the reactor.

Zip files

  1. 1.

    Supplementary Software

    Serial drivers for the pumps and valves written for the hardware described in Supplementary Figure 14.

About this article

Publication history

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Accepted

Published

DOI

https://doi.org/10.1038/nchembio.2318

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