SOLID-PHASE SYNTHESIS OF HUMAN OSTEOCALCIN BY USING A GAMMA-CARBOXYGLUTAMIC ACID-DERIVATIVE

Human osteocalcin, also called bone Gla protein (BGP), consisting of 4 9 amino acids with two to three gamma-carboxyglutamate residues, was c hemically synthesized for the first time by a novel solid-phase peptid e synthesis. An L-enantiomer of yl-gamma,gamma'-dicyclohexyl-gamma-car boxyglutamic acid was designed, prepared and utilized as a monomeric c ompound and proven to be useful for the solid-phase peptide synthesis of human osteocalcin. The synthesis and optical resolution of the gamm a-carboxyglutamic acid (Gla) derivative are first described, followed by the synthesis and characterization of Gla(17)-human osteocalcin. (C ) Munksgaard 1994.