Cyclic phosphatidic acid

Characterization of cyclic PA species as deprotonated species by product-ion ESI-MS in the negative-ion mode after low-energy CID has been conducted [66]. The fragmentation pattern of deprotonated cyclic PA species contains two prominent fragment ions, one corresponding to the product ion of FA substituent of the species (equivalent to the loss of 136 amu) and the other at m/z 153 corresponding to a glycerophosphate derivative. 

and Turk, J. (2009) Electrospray ionization with low-energy collisionally activated dissociation tandem mass spectrometry of glycerophosphoUpids Mechanisms of fragmentation and structural characterization. J. Chromatogr. B 877, 2673-2695. 

and Gross, M.L. (2000) Applications and mechanisms of charge-remote fragmentation. Mass Spectrom. Rev. 19, 398—420. 

Bohrer, A. and Turk, J. (1998) Formation of lithiated addncts of glycerophos-phochohne hpids facilitates their identification by electrospray ionization tandem mass spectrometry. J. Am. Soc. Mass Spectrom. 9,516-526. 

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Fig. 23 Cyclic phosphatidic acids and their carbacyclic analogues...

Yong Xu. Jiang C. Tsukahara, R. Fujiwara, Y. Togyi, C. Prestwich, C.D. Phosphonothioate and fluoromethylene phosphonate analogues of cyclic phosphatidic acid. J. Med. Chem. 2006, 49, 5309-5315. 

Since this discovery, several carba analogs of cyclic phosphatidic acid have been developed. In 2006, Prestwich and coworkers replaced the phosphate ring by cychc mono- and difluorophosphonic acids 3a and 3b... 

Cyclic phosphatidic acid analogs (see Section 2.1, Inhibitors of autotaxin) have also been studied for potential activities on respiratory and cardiovascular functions (06EJP27). Oleyl cPa 8 showed that in anesthetized rats. 

The enantioselective synthesis of phosphonothioate (146) and fluoromethylene phosphonate (147) analogues of cyclic phosphatidic acid, the novel antagonists of lysophosphatidic acid receptors, has been presented. Synthesis of difluoromethy-lene analogue of sphingomyelin (148) in optically active form as a new sphingomyelinase inhibitor has been achieved. The synthesis and biological evaluation of 9-(5, 5 -difluoro-5 -phosphonopentyl)guanine derivatives (149), for use as a purine nucleoside phosphorylase inhibitor, has been described. 

The DAG released has several po.ssible fates. It can he converted to PI. as mentioned, or it can be hydrolyzed furtlicr to release the arachidonic acid component. DAG in conjunction with calcium inn stimulates protein kinase C. By pho<-phoryluting proteins, kinases regulate many cellular activities. The cycle is completed by the phu.sphorylaiion of DAO to phosphatidic acid, which in turn is converted to PI. The complete system remains to be fully understood. Cyclic pho-sphoinositol derivatives appear also to be. secondary me.sscn-gcis. 

B. cereus for the synthesis of glycerol phosphate and dUiydroxyacetonephosphate [159]. Entry IV of Scheme 9 describes the PLD catalyzed hydrolysis of a lyso-phospholipid from which a five-membered ring phosphate is obtained prior to a phosphatase hydrolysis which can give the two isomeric phosphatidic acids. The reaction has been followed by P NMR [ 126]. It appears from this work that in the phospholipase catalyzed hydrolysis of PL bearing free hydroxyl groups in a position suitable for the formation of a 5- or 6-membered cyclic phosphate the... 

Heilman, B., Idahl, L-A, Lernmark, A., Taljedal, I.-B. The pancreatic P-ce recognition of insulin secretagogues Does cyclic AMP mediate the effect of glucose Proc. nat. Acad. Sci. (Wash.) 71, 3405-3409 (1974) Senior,B. Neonatalhypoglycemia.NewEngl.J.Med.289,790-793 (1973) Schneider, P.B. A site of action of thyrotropin. Stimulation of the conversion of glycerophosphate to phosphatidic acid in bovine thyroid slices. J. biol. Chem. 247, 7910-7914 (1972)... 

On the basis of such studies, Hokin proposed a cyclic type of reaction in which sodium combines with phosphatidic acid to yield sodium phosphatidate. Sodium phosphatidate is assumed to be formed at the inner side of the membrane. 

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