L-γ-Carboxyglutamic acid
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L-γ-Carboxyglutamic acid

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γ−Amino Acids
Catalog number
CAS number
Molecular Formula
Molecular Weight
L-γ-Carboxyglutamic acid
(3S)-3-aminopropane-1,1,3-tricarboxylic acid
H-L-Glu(γ-COOH)-OHã-Carboxy-L-glutamic acid
White powder
≥ 99% (TLC)
1.649 g/cm3
Melting Point
176-180 °C (dec.)
Store at-20°C
InChI Key
Canonical SMILES
1. Design and concise synthesis of fully protected analogues of l-gamma-carboxyglutamic acid
Sheng Jiang, Peng Li, Christopher C Lai, James A Kelley, Peter P Roller J Org Chem. 2006 Sep 15;71(19):7307-14. doi: 10.1021/jo061037q.
The design and synthesis of four nonnaturally occurring amino acid analogues of l-gamma-carboxyglutamic acid (Gla), appropriately protected for Fmoc-based solid-phase peptide synthesis (SPPS), is described. These amino acids are Bu-Mal 2, BCAH 3, Pen-Mal 4, and Cm-Gla 5. These Gla analogues have been designed to replace the glutamic acid of position 1 in the cyclic decapeptide G1TE, which is a potent inhibitor of tyrosine kinase, to further enhance binding to the Grb2-SH2 domain of signal transduction receptors. In the new amino acids, the propionic acid side chain of Glu has been replaced by a malonyl or a carboxymethylmalonyl moiety located at different distances from the alpha-carbon to optimize interactions in the phosphotyrosine-binding cavity of the Grb2-SH2 domain. Additionally, a direct and efficient synthetic route for the preparation of Fmoc-protected l-gamma-carboxyglutamic acid, which is amenable to large-scale production, has been developed to provide this important and unique amino acid(1) in 55% overall yield.
2. Oligomerization of L-gamma-carboxyglutamic acid
A R Hill Jr, L E Orgel, J L Bada Orig Life Evol Biosph. 1999 Mar;29(2):115-22. doi: 10.1023/a:1006512304332.
Unlike glutamic acid, L-gamma-carboxyglutamic acid does not oligomerize efficiently when treated with carbonyldiimidazole in aqueous solution. However, divalent ions such as Mg2+ catalyze the reaction, and lead to the formation of oligomers in good yield. In the presence of hydroxylapatite, L-gamma-carboxyglutamic acid oligomerizes efficiently in a reaction that proceeds in the absence of divalent ions but is further catalyzed when they are present. After 'feeding' 50 times with activated amino acid in the presence of the Mg2+ ion, oligomers longer than the 20-mer could be detected. The effect of hydroxylapatite on peptide elongation is very sensitive to the nature of the activated amino acid and the acceptor peptide. Glutamic acid oligomerizes more efficiently than L-gamma-carboxyglutamic acid on hydroxylapatite and adds more efficiently to decaglutamic acid in solution. One might, therefore, expect that glutamic acid would add more efficiently than L-gamma-carboxyglutamic acid to decaglutamic acid on hydroxylapatite. The contrary is true--the addition of L-gamma-carboxyglutamic acid is substantially more efficient. This suggests that oligomerization on the surface of hydroxylapatite depends on the detailed match between the structure of the surface of the mineral and the structure of the oligomer.
3. Enhanced stereoselectivity of a Cu(II) complex chiral auxiliary in the synthesis of Fmoc-L-γ-carboxyglutamic acid
Daniel J Smith, Glenn P A Yap, James A Kelley, Joel P Schneider J Org Chem. 2011 Mar 18;76(6):1513-20. doi: 10.1021/jo101940k. Epub 2011 Feb 3.
L-γ-Carboxyglutamic acid (Gla) is an uncommon amino acid that binds avidly to mineral surfaces and metal ions. Herein, we report the synthesis of N-α-Fmoc-L-γ-carboxyglutamic acid γ,γ'-tert-butyl ester (Fmoc-Gla(O(t)Bu)(2)-OH), a suitably protected analogue for Fmoc-based solid-phase peptide synthesis. The residue was synthesized using a novel chiral Cu(II) complex, whose structure-based design was inspired by the blue copper protein rusticyanin. The five-coordinate complex is formed by Shiff base formation between glycine and the novel ligand (S)-2-(N-(2-methylthio)benzylprolyl)aminobenzophenone in the presence of copper. Michael addition of di-tert-butyl methylenemalonate to the α-carbon of the glycine portion of the complex occurs in a diastereoselective fashion. The resulting (S,S)-complex diastereomer can be easily purified by chromatography. Metal complex decomposition followed by Fmoc protection affords the enantiomerically pure amino acid. With the use of this novel chiral complex, the asymmetric synthesis of Fmoc-Gla(O(t)Bu)(2)-OH was completed in nine steps from thiosalicylic acid in 14.5% overall yield.
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