Oral Presentation 11th Australian Peptide Conference 2015

Chemoselective arylation of amino acids and peptides. (#44)

Frederik Diness 1
  1. University of Copenhagen, Copenhagen, Denmark

Selective chemical protein modification by enzymes is part of Nature’s own tool box for tailoring the properties of biomolecules.[1] Many methods for mimicking these modifications or introducing completely new properties based on selective alkylation or acylation of cysteine or lysine residues have been developed.[2] However, the scope of each of these is typically narrow and a broadly applicable platform for selective chemical protein modification is highly desirable. Towards this goal we have explored chemoselective arylation reactions.[3]

Here we present our recent progress which has proven that this approach may be broadly applied within chemical biology e.g. for functionalization of peptides in aqueous buffer with excellent selectivity. Compared to the existing methods for protein modification this new approach is quite unique as it is simple, irreversible, easy tunable, catalyst-free, versatile, cheap and robust.

The type of chemistry applied is equivalent to cross coupling reactions but cheaper, cleaner and more robust than these. [3,4,5] Hence, this new approach to modifying molecules has a broad scope within molecular science in general.

  1. Walsh, C. Posttranslational modification of proteins: expanding nature's inventory. Roberts and Company Publishers, 2006.
  2. Spicer C D, Benjamin G D Nature Comm. 2014 5
  3. de Araujo A D, Hoang H N, Kok W M, Diness F, Gupta P, Hill T A, Driver R W, Price D A, Liras S, Fairlie D P Angew. Chem. Int. Ed. 2014, 53, 6965-6969.
  4. Diness F, Fairlie, D P Angew. Chem. Int. Ed. 2012, 51, 8012-8016.
  5. Diness F, Begtrup M Org. Lett 2014, 16, 3130-3133.