50848-64-1Relevant articles and documents
Evaluation of a cell penetrating prenylated peptide lacking an intrinsic fluorophore via in situ click reaction
Ochocki, Joshua D.,Mullen, Daniel G.,Wattenberg, Elizabeth V.,Distefano, Mark D.
, p. 4998 - 5001 (2011)
Protein prenylation involves the addition of either a farnesyl (C 15) or geranylgeranyl (C20) isoprenoid moiety onto the C-terminus of many proteins. This natural modification serves to direct a protein to the plasma membrane of the
Total synthesis of geranylgeranylglyceryl phosphate enantiomers: Substrates for characterization of 2,3-O-digeranylgeranylglyceryl phosphate synthase
Zhang, Honglu,Shibuya, Kyohei,Hemmi, Hisashi,Nishino, Tokuzo,Prestwich, Glenn D.
, p. 943 - 946 (2006)
To determine the enantioselectivity of (S)-2,3-di-O-geranylgeranylglyceryl phosphate synthase (DGGGPS) from the thermoacidophilic archaeon Sulfolobus solfataricus, we developed an efficient enantioselective route to the enantiomeric geranylgeranylglyceryl phosphates (R)-GGGP and (S)-GGGP. Previous routes to these substrates involved enzymatic conversions due to the lability of the polyprenyl chains toward common phosphorylation reaction conditions. The synthesis described herein employs a mild trimethyl phosphite/carbon tetrabromide oxidative phosphorylation to circumvent this problem. In contrast to previous results suggesting that only (S)-GGGP can act as the prenyl acceptor substrate, both (R)-GGGP and (S)-GGGP were found to be substrates for DGGGPS.
S-Geranylgeranyl-l-glutathione is a ligand for human B cell-confinement receptor P2RY8
Lu, Erick,Wolfreys, Finn D.,Muppidi, Jagan R.,Xu, Ying,Cyster, Jason G.
, p. 244 - 248 (2019)
Germinal centres are important sites for antibody diversification and affinity maturation, and are also a common origin of B cell malignancies. Despite being made up of motile cells, germinal centres are tightly confined within B cell follicles. The cues that promote this confinement are incompletely understood. P2RY8 is a Gα13-coupled receptor that mediates the inhibition of migration and regulates the growth of B cells in lymphoid tissues1,2. P2RY8 is frequently mutated in germinal-centre B cell-like diffuse large B cell lymphoma (GCB-DLBCL) and Burkitt lymphoma1,3–6, and the ligand for this receptor has not yet been identified. Here we perform a search for P2RY8 ligands and find P2RY8 bioactivity in bile and in culture supernatants of several mouse and human cell lines. Using a seven-step biochemical fractionation procedure and a drop-out mass spectrometry approach, we show that a previously undescribed biomolecule, S-geranylgeranyl-l-glutathione (GGG), is a potent P2RY8 ligand that is detectable in lymphoid tissues at the nanomolar level. GGG inhibited the chemokine-mediated migration of human germinal-centre B cells and T follicular helper cells, and antagonized the induction of phosphorylated AKT in germinal-centre B cells. We also found that the enzyme gamma-glutamyltransferase-5 (GGT5), which was highly expressed by follicular dendritic cells, metabolized GGG to a form that did not activate the receptor. Overexpression of GGT5 disrupted the ability of P2RY8 to promote B cell confinement to germinal centres, which?indicates that GGT5 establishes a GGG gradient in lymphoid tissues. This work defines GGG as an intercellular signalling molecule?that is involved in organizing and controlling germinal-centre responses. As the P2RY8 locus is modified in several other types of?cancer in addition to GCB-DLBCL and Burkitt lymphoma, we speculate that GGG might have organizing and growth-regulatory roles in multiple human tissues.
GGA DERIVATIVES
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Paragraph 0340; 0343, (2015/05/26)
This invention relates to geranylgeranyl acetone (GGA) derivatives, pharmaceutical compositions comprising GGA derivatives and the use of GGA derivatives.