VITAMIN-K-DEPENDENT CARBOXYLATION - SYNTHESIS AND BIOLOGICAL PROPERTIES OF DIASTEREOISOMERIC GAMMA-SUBSTITUTED GLUTAMIC-ACID CONTAINING PEPTIDIC SUBSTRATES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 24  (5) , 505-515
Abstract
Pentapeptides Phe-Leu-X-Glu-Val where X is successively L-threo-.gamma.-fluoro-glutamyl, L-erythro-.gamma.-fluoro-glutamyl, L-threo-.gamma.-methyl-glutamyl or L-erythro-.gamma.-methyl-glutamyl were synthesized and tested as substrates for the vitamin K-dependent carboxylation. L-threo- or L-erythro-.gamma.-methyl-glutamyl were not carboxylated by both corresponding peptides were inhibitors of the reaction. The L-threo-.gamma.-methyl-glutamyl containing peptide had the highest affinity described so far for the active site of the carboxylase (80 .mu.M). In the .gamma.-fluoro-glutamyl series, only the L-eythro-.gamma.-fluoro-glutamyl residue was carboxylated, showing that the enzymatic hydrogen abstraction was stereospecific and corresponds to the elimination of the pro S hydrogen of glutamic acid. The lack of in vitro dicarboxylation of model peptides in contrast with the in vivo polycarboxylation of endogenous precursors was discussed along with the regiospecificity of the reaction with the different substrates. [Phe-Leu-X-Glu-Val was used in place of the endogenous precursors to study the carboxylation process. The role of endogenous peptides as precursors of coagulation factors and bone protein was mentioned.].