L-phosphoserine

Metabolite-membrane interaction may be involved in Alzheimer s disease. The disease is characterized by changes in phospholipid metabolism, which lead to perturbations in the level of phosphomonoesters such as L-phosphoserine (l-PS). It is spec-... 

Figure 19 Reconstruction of 3,P CSA powder spectra of monoanionic (left) and dianionic (right) phosphate groups in lyophilisates of L-phosphoserine prepared with LiOH, NaOH and KOH. Taken from Ref. [75].

Berkowitz. D.B.. Eggen, M., Shen. Q.. and Shoemaker, R.K., Ready access to fluorinated phosphonate mimics of secondary phosphates. Synthesis of the (a,a-dilliioroalkyl)phosphonalc analogues of l-phosphoserine. L-phosphoallothreonine. and L-phosphothreonine, J. Org. Chem., 61, 4666, 1996. 

The first reaction is p-elimination in cysteine, serine, phosphoserine, and threonine residues due to attack by hydroxide ion, leading to the formation of very reactive dehydroalanine (DHA). In a cystine residue, this results in rupturing of the disulfide bond and liberation of a sulfide ion and free sulfur (Figure 13.4). Nucleophilic additions of the s-amino group of the protein-bound lysine to the double bond of DHA residue causes crosslinking of the polypeptide chain. After hydrolysis, a mixture of L-lysino-L-alanine and L-lysino-D-alanine, with probably a small proportion of dl and dd isomers,... 

Figure 16 Experimental (left) and simulated (middle) low spinning speed (to, = 2.0 kHz) CSA sideband manifolds of phosphate groups in L-O-phosphoserine lyophilised from solutions at different pH values. For better visualisation of the changes in the CSA tensor after secondary ionisation, the corresponding simulated static powder spectra are also included (right).Taken from Ref. [74]. Reproduced by permission of The Royal Society of Chemistry.

With regard to selenocysteine biosynthesis in archaea and eukarya, a tRNA has been known for some time, which accepts L-serine and possesses an anticodon complementary to UGA. It shares a number of structural featmes with tRNA from E. coli, such as extended aminoacyl acceptor and D-arms. In eukarya, the serine residue attached to this tRNA can be phosphorylated by a specific kinase and it was first assumed that this tRNA inserts phosphoserine into proteins. However, closer examination revealed that this tRNA carries selenocysteine in vivo and certainly is the pendant to tRNA from E. coli. It is still elusive whether (9-phosphoseryl-tRNA is the biosynthetic intermediate for selenocysteyl-tRNA formation in eukaryotes also, there is no evidence yet of an eukaryal and archaeal enzyme, equivalent in its function to selenocysteine synthase from bacteria. 

Olefination of aldehydes with a-silyl- and a-stannyl-stabilized phosphonate carbanions derived from cyclo-[L-AP4-D-Val] allow a (Z)-selective access to a,p-substituted vinyl phosphonates (343) that have been transformed into enantiomerically pure 4-alkylidene 4PA derivatives (344) (Figure 54). " Electrophilic fluorination of lithiated bis-lactim ethers derived from cyclo-[L-AP4-D Val] (345) with commercial NFSi allow direct access to a-monofluor-inated phosphonate mimetics of naturally occurring phosphoserine (346) and phosphothreonine (347), in enantiomerically pure form and suitably protected for solid-phase peptide synthesis (Figure 55). ... 

Zacharion, M. Traverso, L Hearn, M.T.W. High-performance liquid chromatography of amino acids, peptides and proteins CXXXI. o-Phosphoserine as a new chelating ligand for use with hard Lewis metal ions in the im-mobilized-metal affinity chromatography of proteins. J. Chromatogr. 1993, 646, 107-120. 

KIEs and pH-rate dependencies for V/K were measured for the reactions of the dual-specificity phosphatase VHR177 and the Yersinia PTP178 with the alkyl phosphate mNBP, which, with a leaving group pK l of 14.9, is a better mimic for physiological alkyl phosphate substrates like phosphoserine or phosphothreonine. In... 

A series of addition reactions use the more nucleophilic cerium(III)5 " - or zinc(II) derivatives prepared in situ. Thus, ihe organozinc reagent derived from diethyl l-bromo-1,1-difluoromethylphosphonate reacts smoothly with cx-bromoacrylic acid in THF at room temperature in the presence of catalytic quantities of Cul to give the 1,4-addition product in 33% yield. After several transformations, this is converted into diethyl 3-(hydroxycarbonyl)-3-amino-l,l-difluoro-propylphosphonate, an analogue of phosphoserine (Scheme 3.84). °" ... 

Otaka. A.. Miyoshi. K.. Burke. T.R.. Jr., Roller, P.P., Kubota, H., Tamamura, H., and Fujii, N., Synthesis and apphcation of A-Boc-L-2-amino-4-(diethylphosphono)-4,4-difluorobutanoic acid for solid-phase synthesis of nonhydrolyzable phosphoserine peptide analogues. Tetrahedron Lett., 36, 927, 1995. 

Meyer, H. E., Hoffmann-Posorske, E., and Heihneyer, L. M. G., Determination and location of phosphoserine in proteins and peptides by conversion to S-ethylcysteine, Meth. EnzymoL, 201, 169-185, 1991. 

DOPE l,2-Dioleoyl-sn-glycero-3-phosphoethanolamine DPPC l,2-Dipalmitoyl-SM-glycero-3-phosphocholine DPPS l,2-Dipalmitoyl-s -glycero-3-phosphoserine LB Langmuir-Blodgett MC Monte Carlo... 

POPC l-Palmitoyl-2-oleoyl-s -glycero-3-phosphocholine POPS l-Palmitoyl-2-oleoyl-s -glycero-3-phosphoserine QCM Quartz crystal microbalance RSA Random sequential adsorption SSM Solid supported membrane... 

---