1,3-Dichloroacetone: A Robust Reagent for Preparing Bicyclic Peptides

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    Author
    Lin, Q; Hopper, D; Zhang, H; Qoon, JS; Shen, Z; Karas, JA; Hughes, RA; Northfield, SE
    Date
    2020-02-04
    Source Title
    ACS Omega
    Publisher
    AMER CHEMICAL SOC
    University of Melbourne Author/s
    Northfield, Susan; Karas, John
    Affiliation
    School of Chemistry
    Pharmacology and Therapeutics
    Metadata
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    Document Type
    Journal Article
    Citations
    Lin, Q., Hopper, D., Zhang, H., Qoon, J. S., Shen, Z., Karas, J. A., Hughes, R. A. & Northfield, S. E. (2020). 1,3-Dichloroacetone: A Robust Reagent for Preparing Bicyclic Peptides. ACS OMEGA, 5 (4), pp.1840-1850. https://doi.org/10.1021/acsomega.9b03152.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/254151
    DOI
    10.1021/acsomega.9b03152
    Open Access URL
    http://doi.org/10.1021/acsomega.9b03152
    Abstract
    The chemical synthesis of cyclic peptides is a well-established area of research. This has been further expanded by development of bio-orthogonal reactions that enable access to peptides of greater structural complexity. One approach utilizes 1,3-dichloroacetone to selectively link free cysteine side-chains with an acetone-like bridge via an SN2 reaction. Here, we have used this reaction to dimerize cyclic peptide monomers to create novel bicyclic dimeric peptides. We investigated a range of reaction parameters to identify the optimal dimerization conditions for our model systems. One of the acetone-linked dimeric peptides was analyzed for proteolytic stability in human serum and was observed to still be fully intact after 48 h. This study provides valuable insights into the application of 1,3-dichloroacetone as a tool in the synthesis of complex, multicyclic peptides.

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