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 can be prevented by a coupling/neutralization protocol in the case of Mtt protection or by a tandem deprotection–coupling reaction for the case of the Alloc protection.
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Acknowledgements
We thank Dr. Victor Segarra from Almirall-Prodesfarma for the pKa calculations. M.R. is a ‘Ramon y Cajal’ fellow (MCyT, Spain). This work was partially supported by CICYT (BQU2000-0235), Generalitat de Catalunya (Grup Consolidat, and Centre de Referència en Biotecnologia).
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