Subjects

Addendum to: Nat. Chem. Biol. https://doi.org/10.1038/nchembio.2007, published online 25 January 2016.

In our original Article, we reported the discovery of a chemical probe for the CBX domains of Polycomb repressive complex 1 (PRC1). In subsequent studies undertaken in our laboratories by Kelsey Lamb (Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA), we have observed that our modular synthetic approach detailed in this article leads to epimerization at the alanine position. In the reported synthesis in the original paper, the amide coupling of tripeptide intermediate 13 to tripeptide intermediate 7 for the formation of final product UNC3866 (or for the formation of UNC4219, the amide coupling of tripeptide intermediate 13 to tripeptide intermediate 10) resulted in approximately 40% epimerization at the alanine side chain by NMR. The linear approach outlined in the revised protocol in the Supplementary Note avoids this problem by utilizing a synthetic route in which each amide coupling is performed on the N-Boc-protected amino acid, a method known to diminish epimerization, as validated in our studies by NMR spectra. We note that UNC3866 was originally synthesized using the linear route, despite the modular synthesis reported in the original Supplementary Note, and therefore biological data reported for this compound were not affected. While UNC4219, UNC4007 and UNC4195 were synthesized using the modular route, resynthesis of compounds by the linear route validated that all data obtained using these compounds were unaffected by alanine epimerization. Based on these observations, we provide an alternative synthetic route in this Addendum that avoids alanine epimerization. The protocols have been updated in the Supplementary Note to this Addendum.

Author information

Affiliations

  1. Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNCEshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    • Jacob I Stuckey
    • , Bradley M Dickson
    • , Nancy Cheng
    • , Jacqueline L Norris
    • , Stephanie H Cholensky
    • , Katherine G Huber
    • , Brandi M Baughman
    • , Samantha G Pattenden
    • , Lindsey I James
    •  & Stephen V Frye
  2. Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada

    • Yanli Liu
    • , Wolfram Tempel
    • , Su Qin
    • , Fengling Li
    • , Guillermo Senisterra
    • , Masoud Vedadi
    • , Peter J Brown
    • , Jinrong Min
    •  & Cheryl H Arrowsmith
  3. Department of Epigenetics and Molecular Carcinogenesis, University of Texas MDAnderson Cancer Center, Smithville, Texas, USA

    • Cari Sagum
    • , Karynne Black
    •  & Mark TBedford
  4. National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina at Chapel Hill Medical School, Chapel Hill, North Carolina, USA

    • Xi-Ping Huang
    •  & Bryan L Roth
  5. Department of Pharmacology, University of North Carolina at Chapel Hill Medical School, Chapel Hill, North Carolina, USA

    • Xi-Ping Huang
    •  & Bryan L Roth

Authors

  1. Search for Jacob I Stuckey in:

  2. Search for Bradley M Dickson in:

  3. Search for Nancy Cheng in:

  4. Search for Yanli Liu in:

  5. Search for Jacqueline L Norris in:

  6. Search for Stephanie H Cholensky in:

  7. Search for Wolfram Tempel in:

  8. Search for Su Qin in:

  9. Search for Katherine G Huber in:

  10. Search for Cari Sagum in:

  11. Search for Karynne Black in:

  12. Search for Fengling Li in:

  13. Search for Xi-Ping Huang in:

  14. Search for Bryan L Roth in:

  15. Search for Brandi M Baughman in:

  16. Search for Guillermo Senisterra in:

  17. Search for Samantha G Pattenden in:

  18. Search for Masoud Vedadi in:

  19. Search for Peter J Brown in:

  20. Search for Mark TBedford in:

  21. Search for Jinrong Min in:

  22. Search for Cheryl H Arrowsmith in:

  23. Search for Lindsey I James in:

  24. Search for Stephen V Frye in:

Corresponding authors

Correspondence to Lindsey I James or Stephen V Frye.

Supplementary information

About this article

Publication history

Published

DOI

https://doi.org/10.1038/s41589-019-0242-5