Synthesis of gamma-carboxyglutamic acid-containing peptides by the Boc strategy

gamma-Carboxyglutamic acid (Gla) derivatives having several protecting groups at the gamma-carboxyl function were synthesized and examined for their stabilities and removabilities under the conditions used in peptide synthesis by the Boc strategy. Among them, the cyclohexyl (cHx) group of the Gla residue was found to be stable during the synthesis of the protected peptides, but was quantitatively cleaved by the final HF treatment without decarboxylation. Using Boc-Gla(OcHx)2-OH as a starting material, the synthesis of Gla-containing peptides was achieved by the Boc strategy using a standard HF procedure for the final deprotection.