SEARCH · PubMed Health

Results for “Benzophenones”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources

PubMed2003

Non-thiol farnesyltransferase inhibitors: N-(4-acylamino-3-benzoylphenyl)-3-[5-(4-nitrophenyl)-2-furyl]acrylic acid amides.

We have designed the nitrophenylfurylacryl-substituted benzophenone 4f as a non-thiol farnesyltransferase inhibitor utilizing a novel aryl binding site of farnesyltransferase. Variation of the 2-acylamino substituent at the benzophenone core structure of our initial lead 4f yielded several non-thiol farnesyltransferase inhibitors with improved activity. These compounds display activity in the low nanomolar range.

Alkyl and Aryl Transferases↗

PubMed2002

4-[18F]fluoroarylalkylethers via an improved synthesis of n.c.a. 4-[18F]fluorophenol.

This paper describes the improved synthesis of n.c.a. 4- 18F]fluorophenol for the preparation of 18F-labeled alkylarylethers. Nucleophilic fluorination of substituted benzophenone derivatives yielded n.c.a. 4- 18F]fluoro-4'-substituted benzophenones with 80- 90% RCY, which were converted to benzoic acid phenylesters by treatment with peracetic acid. Strong electron-withdrawing substituents like nitro, cyano and trifluoromethyl favor a fluorophenyl-to-oxygen migration resulting in the formation of corresponding benzoic acid fluorophenylesters. N.c.a. 18F]fluorophenol is almost quantitatively formed after hydrolysis and can easily be converted with alkylhalides into n.c.a. 18F]fluoroarylalkylethers.

Alkanes↗

PubMed2003

Supercritical fluid generated stationary phases for liquid chromatography and capillary electrochromatography.

Chromatographic silica-bonded stationary phases have been prepared using supercritical CO(2) as the reaction medium. (29)Si solid-state NMR spectra of the generated bonded silica phases show unreacted silica species Q(3) and Q(4), alongside important resonances for surface-bound ligands, T(1), T(2), and T(3). Initially, a fluorinated octyl silica (C(8)) phase was produced, by reacting (1)H,(1)H,(2)H,(2)H-perfluorooctyltriethoxysilane with silica particles (3 microm) in sc-CO(2) at 60 degrees C and 450 atm for 3 h. In-house-packed LC columns of this fluorinated sc-C(8) silica phase yielded typical reversed-phase behavior when a standard test mix of benzamide (k' = 1.03), benzophenone (k' = 8.11), and biphenyl (k' = 14.92) was eluted. When packed into fused-silica capillaries for CEC, this fluorinated sc-C(8) silica phase gave linear plots of log k' versus percentage MeOH for benzophenone and biphenyl and, in contrast to octyl or octadecyl silica phases, displayed selectivity for aromatic thioureas when chromatographed among a series of synthetic organic thiourea test solutes. Similarily, an octadecyl silica phase (sc-C(18) silica) was prepared by reaction of n-octadecyltriethoxysilane in sc-CO(2), packed at 9500 psi and examined by LC. The sc-C(18) silica LC column yielded high column efficiency (up to 141 000 N/m (fluorene)) and excellent asymmetry factors (1.06, fluorene) without resource to end-capping. Following a second silylating or end-capping step using hexamethyldisilazane in sc-CO(2), sc-end-capped sc-C(18) silica phases elute N,N-DMA before toluene and the toluidine isomers as a single peak, indicating lowered silanol activity according to the Engelhardt test. A rapid separation of the important pharmaceutical substances, ketoprofen, naproxen, fentoprofen, and ibuprofen, on an sc-end-capped sc-C(18) silica phase is also shown.

Journal Article↗

PubMed2005

Covalent micropatterning of poly(dimethylsiloxane) by photografting through a mask.

A new photografting method to micropattern a covalent surface modification on poly(dimethylsiloxane) (PDMS) provides advantages in simplicity and efficiency. To accomplish the entire process on the benchtop, the PDMS was initially treated with benzophenone dissolved in a water/acetone mixture. This process permitted limited diffusion of the photoinitiator into the PDMS surface. Polymerization of acrylic acid was initiated by exposure of the benzophenone-implanted PDMS to UV radiation through a photomask with a thin aqueous layer of acrylic acid sandwiched between the PDMS and photomask. This procedure resulted in patterned poly(acrylic acid) (PAA) on the PDMS surface. In the modified regions, PAA and PDMS formed an interpenetrating polymer network extending 50 microm into the PDMS with an X-Y spatial resolution of 5 microm. The carboxyl groups of the PAA graft could be derivatized to covalently bond other molecules to the patterned PAA. Two bioanalytical applications of this micropatterned surface were demonstrated: (1) a guide for cell attachment and growth and (2) a substrate for immunoassays. 3T3 cells were shown to selectively localize to modified surface regions where they could be cultured for up to 7 days. Additionally, the micropatterned surface was used to immobilize either protein A or antibody for heterogeneous immunoassays.

Acrylic Resins↗

PubMedDate not supplied

Adenosine 2'-monophosphate, 5'-O-[S-(4-succinimidylbenzophenone)-thiophosphate]: a new photoaffinity label for the coenzyme site of porcine NADP-specific isocitrate dehydrogenase.

A new photoaffinity label, adenosine 2'-monophosphate, 5'-O-[S-(4-succinimidyl-benzophenone)thiophosphate] (2'-P-AMPS-Succ-BP), has been synthesized by an initial thiophosphorylation of 2'-AMP with PSCl(3) to form 2'-AMP-5'-thiophosphate (2'-AMP-5'-SP), followed by a coupling reaction of 2'-AMP-5'-SP with benzophenone-4-maleimide to produce 2'-P-AMPS-Succ-BP. This product and its precursor were characterized by thin-layer chromatography, (31)P NMR, phosphorus analysis, and electron-spray mass spectroscopy. 2'-P-AMPS-Succ-BP functions as a photoaffinity label of porcine NADP-specific isocitrate dehydrogenase. To obtain reaction with other amino acids, Cys269 and Cys379, the most reactive cysteines of this enzyme, were mutated to yield a double mutant enzyme (C269A/C379S) exhibiting comparable activity and kinetic parameters to those of wild-type enzyme. 2'-P-AMPS-Succ-BP inactivates C269A/C379S enzyme upon UV irradiation. The reaction exhibits a nonlinear relationship of k(inact) versus [2'-P-AMPS-Succ-BP] with K(R) = 12 microM and k(max) = 0.0275 min(-1). NADP, NADPH, or 2'-monophospho-adenosine 5'-diphosphoribose protects the enzyme against 2'-P-AMPS-Succ-BP inactivation. The ligand protection studies suggest that 2'-P-AMPS-Succ-BP binds to the porcine enzyme at the site best occupied by NADP/NADPH. The dimeric C269A/C379S isocitrate dehydrogenase incorporates 1.0 mol of 2'-P-[(35)S]AMPS-Succ-BP/mol enzyme dimer concomitant with complete loss of enzyme activity. The new photoaffinity label may be generally useful to identify important amino acid residues of NADP-specific enzymes.

Adenosine↗

PubMed1994

Acceptor helix interactions in a class II tRNA synthetase: photoaffinity cross-linking of an RNA miniduplex substrate.

The 875 amino acid class II Escherichia coli alanine tRNA synthetase aminoacylates hairpin minihelices and miniduplexes comprising complementary base pairs that reconstruct the acceptor helix of alanine tRNA. Aminoacylation is dependent upon a G3:U70 base pair in the tRNA acceptor stem. A synthetic RNA miniduplex with a phosphorothioate internucleotide linkage on the 5'-side of U70 facilitated the stable attachment of a pendant benzophenone to the ribonucleotide backbone. The benzophenone-labeled duplex is active for aminoacylation. Irradiation of the labeled duplex produced a cross-linked RNA protein complex, in which the major site of RNA attachment is the segment between the class II defining sequence motifs 2 and 3. This segment spans a putative zinc-binding motif, which has been implicated in acceptor helix recognition, and is within a 461 amino acid N-terminal fragment that was recently shown to have full activity for minihelix aminoacylation. These results, together with the X-ray crystallographic investigations of the class II aspartate tRNA synthetase-tRNA(Asp) complex, suggest that the segment between motifs 2 and 3 in the 10 class II synthetases contributes generally to the docking of tRNA acceptor helices. The sequence diversity of this segment implies that its mode of interaction with the acceptor helix is idiosyncratic to the class II enzyme.

Affinity Labels↗

PubMed2002

Identification of the principal binding site for RGD-containing ligands in the alpha(V)beta(3) integrin: a photoaffinity cross-linking study.

By superimposing data obtained by photo-cross-linking RGD-containing ligands to the human alpha(V)beta(3) integrin onto the crystal structure of the ectopic domain of this receptor (Xiong et al. (2001) Science 294, 339-345), we have identified the binding site for the RGD triad within this integrin. We synthesized three novel analogues of the 49-amino acid disintegrin, echistatin: [Bpa(21),Leu(28)]-, [Bpa(23),Leu(28)]-, and [Bpa(28)]echistatin. Each contains a photoreactive p-benzoyl-phenylalanyl (Bpa) residue in close proximity to the RGD motif which spans positions 24-26; together, the photoreactive positions flank the RGD motif. The analogues bind with high affinity to the purified recombinant alpha(V)beta(3) integrin, but very poorly to the closely related human alpha(IIb)beta(3) platelet integrin. While echistatin analogues containing Bpa in either position 23 or 28 cross-link specifically and almost exclusively to the beta(3) subunit of alpha(V)beta(3), [Bpa(21),Leu(28)]echistatin cross-links to both the alpha(V) and the beta(3) subunits, with cross-linking to the former favored. [Bpa(23),Leu(28)]echistatin cross-links 10-30 times more effectively than the other two analogues. We identified beta(3)[109-118] as the domain that encompasses the contact site for [Bpa(28)]echistatin. This domain is included in beta(3)[99-118] (Bitan et al. (2000) Biochemistry 39, 11014-11023), a previously identified contact domain for a cyclic RGD-containing heptapeptide with a benzophenone moiety in a position that is similar to the placement of the benzophenone in [Bpa(28)]echistatin relative to the RGD triad. Recently, we identified beta(3)[209-220] as the contact site for an echistatin analogue with a photoreactive group in position 45, near the C-terminus of echistatin (Scheibler et al. (2001) Biochemistry 40, 15117-14126). Taken together, these results support the hypothesis that the very high binding affinity of echistatin to alpha(V)beta(3) results from two distinct epitopes in the ligand, a site including the RGD triad and an auxiliary epitope at the C-terminus of echistatin. Combining our results from photoaffinity cross-linking studies with data now available from the recently published crystal structure of the ectopic domain of alpha(V)beta(3), we characterize the binding site for the RGD motif in this receptor.

Amino Acid Sequence↗

PubMedDate not supplied

The polymer-supported phospholipid bilayer: tethering as a new approach to substrate-membrane stabilization.

We present a new molecular engineering approach in which a polymer-supported phospholipid bilayer is vertically stabilized by controlled covalent tethering at both the polymer-substrate and polymer-bilayer interfaces. This approach is based on lipopolymer molecules, which not only form a polymer cushion between the phospholipid bilayer and a solid glass substrate but also act as covalent connections (tethers) between the bilayer and cushion. Our approach involves Langmuir-Blodgett transfer of a phospholipid-lipopolymer monolayer followed by Schaefer transfer of a pure phospholipid monolayer and is capable of varying the tethering density between the polymer layer and the phospholipid bilayer in a very controlled manner. Further stabilization is achieved if the glass substrate is surface-functionalized with a benzophenone silane. In this case, a photocross-linking reaction between the polymer and benzophenone group allows for the covalent attachment of the polymer cushion to the glass substrate. This approach is similar to that recently reported by Wagner and Tamm in which double tethering is achieved via lipopolymer silanes (Wagner, M. L.; Tamm, L. K. Biophys. J. 2000, 79, 1400). To obtain a deeper understanding of how the covalent tethering affects the lateral mobility of the bilayer, we performed fluorescence recovery after photobleaching (FRAP) experiments on polymer-tethered bilayers at different tethering densities (lipopolymer/phospholipid molar ratios). The FRAP data clearly indicate that the hydrophobic lipopolymer moieties act as rather immobile obstacles within the phospholipid bilayer, thereby leading to hindered diffusion of phospholipids. Whereas the high lateral diffusion coefficient of D = 17.7 mum(2)/s measured at low tethering density (5 mol % lipopolymer) indicates rather unrestricted motion within the bilayer, corresponding values at moderate (10 mol % lipopolymer) and high (30 mol % lipopolymer) tethering densities of D = 9.7 mum(2)/s and D = 1.1 mum(2)/s, respectively, show significant hindered diffusion. These results are contrary to the recent findings on similar membrane systems reported by Wagner and Tamm in which no significant change in phospholipid diffusion was found between 0 and 10 mol % lipopolymer. Our experimental report leads to a deeper understanding of the complex problem of interlayer coupling and offers a path toward a compromise between stability of the whole system and lateral mobility within the bilayer. Furthermore, the FRAP measurements show that polymer-tethered membranes are very interesting model systems for studying problems of restricted diffusion within two-dimensional fluids.

Diffusion↗

PubMed2002

Mechanistic studies on the B(C(6)F(5))(3) catalyzed allylstannation of aromatic aldehydes with ortho donor substituents.

Mechanistic studies on the B(C(6)F(5))(3) catalyzed allylstannation of isomeric substituted benzaldehydes are reported. Confirming a report by Maruoka et al., good (5:1) to excellent (>20:1) selectivities for ortho over para isomers are observed when 1:1 mixtures (X = OMe, Cl, F, OTBS) are allylstannated with C(3)H(5)SnBu(3) in the presence of B(C(6)F(5))(3) (2.5% per CHO). The best selectivities are observed for the anisaldehydes. Multinuclear NMR studies on solutions of B(C(6)F(5))(3) and C(3)H(5)SnBu(3) (1:1 to 1:5) show that the borane abstracts the allyl group from the organotin reagent, forming an adduct (C(6)F(5))(3)B...CH(2)CHCH(2)SnBu(3), 1, or ion pair [(C(6)F(5))(3)BCH(2)CH=CH(2)](-)[Bu(3)SnCH(2)CHCH(2)SnBu(3)](+), 2, depending on the reagent ratio. These compounds are important in the mechanism of Lewis acid catalyzed 1,3-isomerization of substituted allyl stannanes. When allyltin reagent is added to solutions of B(C(6)F(5))(3) and ortho-anisaldehyde (1:5) at -60 degrees C, conversion to the stannylium ion pair [Bu(3)Sn(ortho-anisaldehyde)(2)](+)[o-ArCH(allyl)OB(C(6)F(5))(3)](-), o,o-4, is observed. The structure of this species was confirmed by (1)H, (11)B, (19)F, and (119)Sn NMR spectroscopy and by forming related ion pairs (o-5 and o,o-5) utilizing the [B(C(6)F(5))(4)](-) counteranion via reaction of [Bu(3)Sn](+)[B(C(6)F(5))(4)](-) with aldehyde. The anion in o,o-4 is formed via direct allylation of the ortho-anisaldehyde/B(C(6)F(5))(3) adduct o-3, while the cation arises upon aldehyde ligation of the resulting tributylstannylium ion. The crystal structure of the related derivative ortho-C(6)H(4)(OMe)CHO x SnMe(3)BF(4), 6, showed that the aldehyde binds the tin nucleus only through the carbonyl oxygen. Similar reactions using para-anisaldehyde show that formation of p,p-4 occurs at a much slower rate, again demonstrating the preference for the ortho substituted substrates. For similar experiments using benzophenone, however, formation of the ion pair [Bu(3)Sn(Ph(2)CO)(2)](+)[(C(3)H(5))B(C(6)F(5))(3)](-), 8, was observed, illustrating the differences subtle changes in substrate can bring. Ion pair 8 is formed via the trapping of 1 by the benzophenone substrate. In the presence of excess aldehyde and allyltin reagent, ion pair o,o-4 catalyzes the allylstannation of aldehyde to give the product stannyl ether. Several lines of experimental evidence suggest this is the true catalyst in the system. The chemoselectivity observed thus does not rely on classical chelation control in any way. Rather, we propose that the ortho donor group stabilizes the developing positive charge at the beta carbon of the allyl group and the tin atom during the allylation event. This stabilization renders the ortho substituted substrates kinetically favored toward allylation irrespective of the Lewis acid employed.

Journal Article↗

PubMed2004

Mechanism of stereo- and regioselectivity in the Paternò-Büchi reaction of furan derivatives with aromatic carbonyl compounds: importance of the conformational distribution in the intermediary triplet 1,4-diradicals.

Temperature and substituent effects on the stereo- and regioselectivity have been investigated in the photochemical [2 + 2] cycloaddition reaction, the so-called Paternò-Büchi (PB) reaction, of unsymmetrically substituted furans 2a,b (2-methyl- and 3-methylfuran) with aromatic carbonyl compounds 1a,b (benzaldehyde and benzophenone). The regio-random but stereoselective (exo/endo > 97/3) formation of lower substituted oxetane 3a and higher substituted oxetane 4a is found in the reaction with benzaldehyde (1a). The exclusive stereoselectivity is not dependent on the position of methyl substituent on the furan ring and the reaction temperature. The double-bond selection (3a versus 4a) is slightly dependent on the reaction temperature (3a/4a = 55/45 to 40/60). The Eyring plots of the regioselectivity are linear. Contrastively, in the reaction with benzophenone (1b), the double-bond selection (3b versus 4b) largely depends on the reaction temperature. The Eyring plots are not linear, but the inflection points are observed. The transient absorption spectroscopic analyses (picosecond time scale) clarify the intervention of triplet 2-oxabutane-1,4-diyls in the photochemical processes. Computational studies reveal the equilibrium structures of the triplet diradicals, energy barriers between the conformers, and the equilibrium constants. A rational mechanism is herein proposed by the support of both experimental and computational investigations to account for not only the exclusive formation of the exo-configured oxetanes 3a and 4a but also the nonlinear Eyring plots observed in the reaction with 1b.

Journal Article↗

PubMed2006

Transglutaminase-catalyzed site-specific conjugation of small-molecule probes to proteins in vitro and on the surface of living cells.

Site-specific protein labeling methods allow cell biologists to access the vast array of existing chemical probes for the study of specific proteins of interest in the live cell context. Here we describe the use of the transglutaminase enzyme from guinea pig liver (gpTGase), whose natural function is to cross-link glutamine and lysine side chains, to covalently conjugate various small-molecule probes to recombinant proteins fused to a 6- or 7-amino acid transglutaminase recognition sequence, called a Q-tag. We demonstrate labeling of Q-tag fusion proteins both in vitro and on the surface of living mammalian cells with biotin, fluorophores, and a benzophenone photoaffinity probe. To illustrate the utility of this labeling, we tagged the NF-kappaB p50 transcription factor with benzophenone, cross-linked with UV light, and observed increased levels of p50 homodimerization in the presence of DNA and the binding protein myotrophin.

Animals↗

PubMed2006

A well-defined hydrocarbon-soluble calcium hydroxide: synthesis, structure, and reactivity.

Controlled hydrolysis of a (beta-diketiminate)calcium-amide gave a heteroleptic (beta-diketiminate)calcium-hydroxide complex that is remarkably stable against ligand exchange and formation of Ca(OH)2. The structure of this dimeric complex shows OH- units that symmetrically bridge the Ca2+ ions. This hydrocarbon-soluble calcium hydroxide reacted rapidly with CO2 to produce a gel from which amorphous CaCO3 slowly separated. This reaction behavior allows for sol-gel coating with CaCO3 from an organic solvent. Reaction with benzophenone did not lead to nucleophilic attack of OH- to the carbonyl but gave a red benzophenone adduct instead.

Journal Article↗

PubMed1999

Structure--activity relationships of lysophosphatidic acid: conformationally restricted backbone mimetics.

Lysophosphatidic acid (LPA) has associated with it an intriguing cell biology that is thought to be mediated through its interaction with G-protein coupled receptor(s). In an effort to extend the structure-activity relationships of LPA, we have produced a series of LPA analogues in which the glycerol core in LPA was replaced with conformationally restricted aryl substructures. The aryl substructures encompassed aminophenol, resorcinol, dihydroxy benzophenone, and tocopherol systems. The benzophenone moiety was investigated both as a conformationally restricting substructure for LPA and as a possible photoreactive alkylating agent for the LPA receptor(s). All LPA analogues were evaluated for their potency and efficacy in mobilizing calcium ions from internal stores in MDA MB-231 cells. Ten of the 14 analogues exhibited activity in this assay at doses up to 5 microM; none of the compounds exhibited nonreceptor-mediated lytic activity at this maximal concentration. The receptor response showed surprising tolerance for manipulation in the backbone region of LPA, although none of the compounds were equipotent to LPA. This tolerance for a variety of structures has given us new leads into the realization of novel agonists and antagonists of the LPA receptor(s).

Calcium↗

PubMed2002

Spectral properties and reactivity of diarylmethanol radical cations in aqueous solution. Evidence for intramolecular charge resonance.

Spectral properties and reactivities of ring-methoxylated diarylmethane and diarylmethanol radical cations, generated in aqueous solution by pulse and gamma-radiolysis and by the one-electron chemical oxidant potassium 12-tungstocobalt(III)ate, have been studied. The radical cations display three bands in the UV, visible, and vis-NIR regions of the spectrum. The vis-NIR band is assigned to an intramolecular charge resonance interaction (CR) between the neutral donor and charged acceptor rings, as indicated by the observation that the relative intensity of the vis-NIR band compared to that of the UV and visible bands does not increase with increasing substrate concentration and that the position and intensity of this band is influenced by the ring-substitution pattern. In acidic solution (pH = 4), monomethoxylated diarylmethanol radical cations 1a.(+ -)1e.(+) decay by C(alpha)-H deprotonation [k = (1.7-1.9) x 10(4)s(-1)] through the intermediacy of a ketyl radical, which is further oxidized in the reaction medium to give the corresponding benzophenones, as evidenced by both time-resolved spectroscopic and product studies. With the dimethoxylated radical cation 2.(+), C(alpha)-H deprotonation is instead significantly slower (k = 6.7 x 10(2)s(-1)). In basic solution, 1a.(+)-1e.(+) undergo (-)OH-induced deprotonation from the alpha-OH group with k(OH.)approximately equal to 1.4 x 10(10)M(-1)s(-1), leading to a ketyl radical anion, which is oxidized in the reaction medium to the corresponding benzophenone.

Journal Article↗

PubMed2003

Unexpected differences in the alpha-halogenation and related reactivity of sulfones with perhaloalkanes in KOH-t-BuOH.

Most alkyl phenyl sulfones are readily alpha-chlorinated with CCl(4) and alpha-brominated with CBrCl3 in KOH-t-BuOH via radical-anion radical pair (RARP) reactions. While isopropyl mesityl sulfone (4) is easily alpha-chlorinated with CCl(4), it was completely recovered when treated with the more reactive CBrCl3. Subsequent investigations showed the latter result to be due to the poor acidity of 4 together with the rapid depletion of CBrCl3 and KOH by their reaction with each other, and led to a variety of other important results. 4-Hydroxyphenyl isopropyl sulfone (6) is unreactive with either CCl4 or CBrCl3 in KOH-t-BuOH, its phenoxide anion strongly reducing the electronegativity of the sulfonyl group, thereby inhibiting alpha-anion formation. This effect is reversed by the electron-withdrawing influence of two alpha-phenyls, so that benzhydryl 4-hydroxyphenyl sulfone (8) is readily alpha-halogenated in KOH-t-BuOH with CCl4 or CBrCl3. On further contact with KOH-t-BuOH the alpha-halogenated sulfones from 8 are decomposed into benzophenone and phenol. While the alpha-halogenated derivatives of 4-methoxyphenyl benzhydryl sulfone (9) are stable to base, they are decomposed even under mildly acidic conditions into 4-methoxyphenyl 4-methoxybenzenethiolsulfonate (9c), phenol, and benzophenone. Mono-alpha-halogenation of benzyl phenyl sulfone (10) enhances the rate of the subsequent halogenation, so that alpha,alpha-dihalogenation is attained while much substrate is still present and the mono-alpha-halogenated product is not detected. The ease of reductive debromination of alpha-bromo sulfones with Cl3C- was correlated with the stability of the formed alpha-anions, explaining the success with alpha-bromobenzylic sulfones but failure with alpha-bromoalkyl sulfones. In the presence of air and the absence of competing halogenation, formation of the alpha-anions of alkyl aryl sulfones is quickly accompanied by oxidative cleavage by atmospheric O2, leading to the formation of arenesulfonyl alcohols, arenesulfonyl halides, and haloarenes.

Journal Article↗

PubMed2004

An antenna-sensitized nitroindoline precursor to enable photorelease of L-glutamate in high concentrations.

1-Acyl-7-nitroindolines are useful reagents for rapid release of carboxylates upon flash photolysis in aqueous solution and have been particularly effective for rapid (submicrosecond) release of neuroactive amino acids such as l-glutamate in biological experiments. In model systems the efficiency of photorelease has been shown to be greatly improved by attachment of a benzophenone triplet-sensitizing antenna. The present work describes synthesis and initial biological evaluation of the l-glutamate precursor 3. A significant improvement in the overall synthesis uses double Boc protection of the glutamate amino group to avoid side reactions during introduction of the nitro group. To accommodate the multiple functionalities in 3, linkage of the nitroindoline and benzophenone moieties is carried out late in the synthesis. Photolysis of 3 occurs with near-quantitative stoichiometry and the released l-glutamate efficiently activates neuronal glutamate ion channels.

Glutamic Acid↗

PubMed2005

Synthesis of a photoactivatable (2S,3R)-sphingosylphosphorylcholine analogue.

The receptor for the lipid mediator sphingosylphosphorylcholine (SPC) has not yet been identified. We describe here the synthesis of the first photoaffinity analogue of SPC. This probe, which contains a 14C-isotopic label in the choline methyl groups and a photoreactive benzophenone in the long-chain base, may be a useful tool in the identification of the G protein coupled receptors that have been postulated to interact directly and specifically with SPC and in the definition of the ligand-binding sites. The key steps in the synthesis are selective reduction of the triple bond in enyne 6 to install the 4E double bond, Suzuki coupling to incorporate the benzophenone photophore at the end of the sphingoid chain, and reduction of the 2-azidoethyl phosphate headgroup of 13 followed by N,N,N-trimethylation to introduce the radiolabel into the choline moiety. The synthesis was completed by the release of the amino group at C2 of the sphingoid base of SPC analogue 2.

Carbon Isotopes↗

PubMed2006

Synthesis of photoactivatable analogues of lysophosphatidic acid and covalent labeling of plasma proteins.

[reaction: see text] Lysophosphatidic acids bearing a benzophenone group in either the sn-1 or sn-2 chain of an oleoyl-type ester or oleyl-type ether chain and (32)P in the phosphate group were synthesized. The benzophenone moiety was introduced by selective hydroboration of the double bond of enyne 11 at low temperature, followed by a Suzuki reaction with 4-bromobenzophenone. The key intermediates for the preparation of ester-linked lysophosphatidic acid (LPA) 1 and 3 were obtained in one pot by a modified DIBAL-H reduction of orthoformate intermediate 22. These probes were shown to covalently modify a single protein target in rat plasma containing albumin and several protein targets in rat plasma containing a low level of albumin.

Ethers↗