D. Rich, M. Kawai, H. L. Goodman
Jan 12, 2009
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0
Influential Citations
9
Citations
Journal
International journal of peptide and protein research
Abstract
The synthesis of two analogs of sequence 18-23 of bovine prothrombin precursor is described. Hexapeptides Boc-Cys (Acm)-Leu-Glu(OBzl)-Glu(OBzl)-Pro-Cys (Acm)-OBzl and Ac-Cys(Acm-Leu-Glu(OBzl)-Glu(OBzl)-Pro-Cys(Acm)-OMe were synthesized in solution by stepwise addition of Boc-amino acids using dicyclohexylcarbodiimide/N-hydroxybenzotriazole as the coupling reagent. The acetamidomethyl groups were cleaved and oxidized, using iodine in methanol, to the protected cyclic disulfide in 62-69% yield. The O-benzyl groups were removed either by treatment with anhydrous hydrogen fluoride or hydrogen bromide in trifluoroacetic acid to give the cyclic hexapeptide disulfides, R1-Cys-Leu-Glu-Glu-Pro-Cys-OR2 where R1 - H or Ac and R2 = H or CH3. The cyclic hexapeptides were evaluated as substrates for vitamin K-dependent carboxylase. Both peptides are unusually poor substrates for the carboxylase, and each appears to inhibit carboxylation of Phe-Leu-Glu-Glu-Leu, a good substrate for the enzyme.