Vitamin K dependent carboxylation: synthesis and biological properties of tetrazolyl analogues of pentapeptidic substrates.
The pentapeptides Phe-Leu-X-Glu-Val and Phe-Leu-X-X-Val, where X = 4-(5H-tetrazolyl)-2-aminobutyric acid (tetrazolyl analogue of glutamic acid), were synthesized by addition of tri-n-butyltin azide to the corresponding nitrile-containing peptides. These tetrazolyl peptides and a dinitrile precursor were tested as possible substrates and inhibitors of the vitamin K dependent carboxylation. Phe-Leu-X-Glu-Val was carboxylated (40% of the reference peptide Phe-Leu-Glu-Glu-Val, Km = 20 mM) exclusively on the glutamyl residue, whereas the dinitrile precursor and Phe-Leu-X-X-Val were not carboxylated. The latter was a competitive inhibitor with an affinity (Ki = 3 mM) close to that of the reference peptide (Km = 3 mM).
D015055:1-Carboxyglutamic Acid / Q000096:biosynthesis*; D004578:Electron Spin Resonance Spectroscopy; D005971:Glutamates / Q000096:biosynthesis*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014812:Vitamin K / Q000502:physiology*
D005971:Glutamates; D009842:Oligopeptides; D014812:Vitamin K; D015055:1-Carboxyglutamic Acid