Undesired removal of the Fmoc group by the free ε-amino function of a lysine residue

In solid-phase peptide synthesis, a side-reaction consisting of the premature and undesired removal of the Fmoc group has been detected. This can be caused by a primary amine of sufficient basicity, such as the ε-amino of the Lys, present in the peptide resin. This side-reaction, which is not promoted by either the β-amino side-chain of the Dapa residue or the α-amino group, can be prevented by a coupling/neutralization protocol in the case of Mtt protection or by a tandem deprotection–coupling reaction in the case of Alloc protection. The same kind of side-reaction has been detected when amino side-chain functions of Orn or Daba are free in the peptide resin.