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Fmoc chemistry (revision 1)

Old revision·09:00, 9 Jul 2024·RepackRadek

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Fmoc chemistry
Temporary groupFluorenylmethyloxycarbonyl (Fmoc), base-labile
Side-chain groupsAcid-labile (tBu, Trt, Pbf)
Deprotection reagentPiperidine in DMF
Final cleavageTrifluoroacetic acid with scavengers
Analytical method infobox · conventions

Fmoc chemistry is the protecting-group scheme that dominates modern solid-phase peptide synthesis. The temporary N-terminal group, fluorenylmethyloxycarbonyl, is removed by base; the side-chain protecting groups are removed by acid. The two are orthogonal, so each can be removed without disturbing the other.[1]

Its predecessor, Boc chemistry, used acid for both and therefore required a much stronger acid for final cleavage — hydrogen fluoride — with the handling requirements that implies. Boc chemistry was the scheme of the original solid-phase method.[2] Orthogonality is what made peptide synthesis a routine operation.[1]

References

  1. ^ a b Behrendt R, White P, Offer J. "Advances in Fmoc solid-phase peptide synthesis." Journal of Peptide Science 22(1):4–27 (2016). PMID 26785684.
  2. ^ Merrifield RB. "Solid phase peptide synthesis. I. The synthesis of a tetrapeptide." Journal of the American Chemical Society 85(14):2149–2154 (1963). DOI:10.1021/ja00897a025.