Gamma-carboxylation

K, O2, and C02 (Figure 6.6)., The carboxylation of glutamic acid residues of these proteins appears to be directed by a specific recognition sequence, which is often found in the propeptide to insure binding to the vitamin K-dependent carboxylase. Furie et al., (1999) identified five requirements for gamma carboxylation ... 

Gamma carboxylation of glutamic acid residue in a protein. This is an enzymic reaction catalyzed by a carboxylase to modify a glutamic acid residue of a protein to form qamma-carboxyqlutamic acid. The carboxylase reaction requires vitamin K, 02, and C02. 

Binkley NC, Krueger DC, Engelke JA, Foley AL, and Suttie JW (2000) Vitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults. American Journal of Clinical Nutrition 72,1523-8. 

Grinnell, B.W., Berg, D.T., Walls, J., and Yan, S.B. (1987). Trans-activated expression of fully gamma-carboxylated recombinant human protein C, an anti thrombotic factor. Bio/Technology 5,1189 1192. 

Lipsky JJ. Mechanism of the inhibition of the gamma-carboxylation of glutamic acid by N-methylthiotetrazole-containing antibiotics. Proc Natl Acad Sci USA 1984 ... 

Vecsler M, Loebstein R, Almog S, et al. Combined genetic profiles of components and regulators of the vitamin K-dependent gamma-carboxylation system affect individual sensitivity to warfarin. Thromb Haemost 2006 95(2) 205-ll. 

Zhang N, Li B-Q, Gao S, Ruan J-S, Cai Y-D (2012) Computational prediction and analysis of protein [gamma]-carboxylation sites based on a random forest method. Mol Bio Syst 8 2946-2955... 

Apart from clotting factor proteins, vitamin K-dependent proteins include a variety of regulatory proteins. One of them, the matrix Gla-protein (MGP), through gamma carboxylation of glutamic acid residues, enables it to inhibit extraosseous calciflcation. Vascular calciflcation with its accompanying increased morbidity and mortality is associated with vitamin K deficiency, suggesting a favorable effect of vitamin K on vascular calcification. 

CT-2103 is synthesized by converting Na-PG from its salt form to its protonated form followed by formation of an ester between the gamma carboxylate of the polymer and the 2 alcohol of pacMtaxel. A minor modification of combiiung the 2 steps via in situ formation of the PG add has been investigated with success. Carbodiimide coupling catalysed by DMAP was chosen as the appropriate reagent. Based on solubiMty, DMF was chosen as the reaction solvent. 

Ohsawa, K., Kimura, M., Kurosawa-Ohsawa, K., Takahashi, M., Koyama, M., Abiko, Y, Hirahara, K., Matsuishi, T., and Tanaka, S., 1988, Purification of sufficiently gamma-carboxylated recombinant protein C and its derivatives. Calcium-dependent affinity shift in immunoaffinity and ion exchange chromatography, J. Chromatography 597 285-291. 

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