- Development of isotope-enriched phosphatidylinositol-4- And 5-phosphate cellular mass spectrometry probes
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Synthetic phosphatidylinositol phosphate (PtdInsPn) derivatives play a pivotal role in broadening our understanding of PtdInsPnmetabolism. However, the development of such tools is reliant on efficient enantioselective and regioselective synthetic strategies. Here we report the development of a divergent synthetic route applicable to the synthesis of deuterated PtdIns4Pand PtdIns5Pderivatives. The synthetic strategy developed involves a key enzymatic desymmetrisation step using Lipozyme TL-IM. In addition, we optimised the large-scale synthesis of deuteratedmyo-inositol, allowing for the preparation of a series of saturated and unsaturated deuterated PtdIns4Pand PtdIns5Pderivatives. Experiments in MCF7 cells demonstrated that these deuterated probes enable quantification of the corresponding endogenous phospholipids in a cellular setting. Overall, these deuterated probes will be powerful tools to help improve our understanding of the role played by PtdInsPnin physiology and disease.
- Joffrin, Amélie M.,Saunders, Alex M.,Barneda, David,Flemington, Vikki,Thompson, Amber L.,Sanganee, Hitesh J.,Conway, Stuart J.
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p. 2549 - 2557
(2021/03/01)
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- The fatty acid composition of diacylglycerols determines local signaling patterns
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Caged compounds are designed to release biologically active signaling molecules with temporal, spatial, and even subcellular resolution. But how localized does the signal stay? Using the example of diacylglycerol, some signal responses (PKC) are shown to
- Nadler, Andre,Reither, Gregor,Feng, Suihan,Stein, Frank,Reither, Sabine,Mueller, Rainer,Schultz, Carsten
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p. 6330 - 6334
(2013/07/05)
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- Regioselective approach to phosphatidylinositol 3,5-bisphosphates: Syntheses of the native phospholipid and biotinylated short-chain derivative
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Figure presented A selective bis-silylation of 1D-O-TBDPS-myo-inositol leads to a 1,3,5-trisubstituted inositol, which can be advanced to the headgroup of phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2]. A mild, regioselective method for construction of the diacylglycerol moiety containing differing fatty acid chains, including the naturally occurring lipids, was developed. Their union in the synthesis of the cell-signaling molecule PI(3,5)P2 containing the sn-1-stearoyl and sn-2-arachidonoyl groups is described. The methodology was also used to generate dioctanoyl-PI(3,5)P 2 and a previously unreported biotin-PI(3,5)P2 conjugate, which was coupled to neutravidin beads and used to pull down PI(3,5)P 2-binding proteins from the cytosolic extract of adrenal neurosecretory cells. We report the specific pull-down of the PI(3,5)P 2-binding protein svp1p, a known PI(3,5)P2 effector involved in membrane trafficking.
- Anderson, Regan J.,Osborne, Shona L.,Meunier, Frederic A.,Painter, Gavin F.
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supporting information; experimental part
p. 3541 - 3551
(2010/09/03)
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- The total synthesis of 2-O-arachidonoyl-1-O-stearoyl-sn-glycero-3-phosphocholine-1,3,1′-13C3 and -2,1′-13C2 by a novel chemoenzymatic method
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2-O-Arachidonoyl-1-O-stearoyl-sn-glycero-3-phosphocholine was synthesized with carbon-13 enrichment of the three glycerol carbons and the carbonyl of the stearoyl group. Phospholipase A2 was utilized to give optically pure lyso-PC, and only 3% acyl migration occurred during reacylation with arachidonic acid anhydride. This phospholipid is an important biosynthetic precursor of arachidonic acid metabolites as well as the endocannabinoid 2-arachidonoylglycerol (2-AG), and is now available for NMR studies.
- Duclos Jr., Richard I.
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experimental part
p. 102 - 109
(2010/06/19)
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- First synthesis of natural phosphatidyl-β-d-glucoside
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Herein, we report the chemical synthesis of naturally occurring mammalian phosphatidyl-β-d-glucoside (PtdGlc), in order to confirm the proposed structure and to clarify its stereochemistry. We designed a convergent synthetic strategy, suitable to prepare
- Greimel, Peter,Ito, Yukishige
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p. 3562 - 3566
(2008/09/19)
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- Comprehensive and uniform synthesis of all naturally occurring phosphorylated phosphatidylinositols
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Studies of cellular signal transduction mechanisms involving receptor-mediated generation of inositol phosphates and phosphorylated phosphatidylinositols require easy access to these naturally occurring products. Although numerous synthetic methods have been developed during the past decade, most of these methods suffer from excessive length and lack of generality. In this work we describe the comprehensive and uniform synthesis of all naturally occurring phosphatidylinositols such as phosphatidylinositol, phosphatidylinositol 3-phosphate, 4-phosphate, 5-phosphate, 3,4-bisphosphate, 3,5-bisphosphate, 4,5-bisphosphate, and 3,4,5-trisphosphate, featuring both saturated and unsaturated fatty acid chains.
- Kubiak, Robert J.,Bruzik, Karol S.
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p. 960 - 968
(2007/10/03)
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- Synthesis of naturally occurring phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] and its diastereoisomers
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The chemical synthesis of naturally occurring phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3] and its diastereoisomers was discussed. In the first stage, the preparation of the required enantiomeric 1,2-di-O-acylglycerol derivatives was done. The second stage involved the preparation of suitably protected enantiomeric myo-inositol 1-phosphates. The glycerol and inositol building blocks were coupled together and the 3-, 4- and 5-hydroxy functions of the inositol residues in the coupled products were phosphorylated. Finally, the protecting groups were removed to give PtdIns(3,4,5)P3 and its diastereoisomers.
- Gaffney, Piers R.J.,Reese, Colin B.
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p. 192 - 205
(2007/10/03)
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- Preparation of 2-O-arachidonoyl-1-O-stearoyl-sn-glycerol and other di-O-acyl glycerol derivatives
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R(-)-2,3- and S(+)-1,2-O-Isopropylidene-sn-glycerols (4 and 9) are converted into 2-O-arachidonoyl-1-O-stearoyl and 2-O-arachidonoyl-3-O-stearoyl-sn-glycerols (2 and 3, respectively); glycerol is also converted into its racemic 1,2- and its symmetrical 13-di-O-linoleoyl derivatives (14 and 17, respectively).
- Gaffney, Piers R.J.,Reese, Colin B.
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p. 2539 - 2542
(2007/10/03)
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- Cosmetic composition
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A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamine derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.
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- Cosmetic composition containing DOPA derivatives
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A composition for topical application to human hair or skin contains a chemical analogue of dihydroxyphenyl alanine (DOPA). This chemical analogue can be absorbed by skin or by a hair follicle and metabolised in-vivo, thus leading to the formation of melanin in skin or to the growth of melanin-pigmented hair. Consequently the composition can give controlled skin darkening to mimic sun-induced tanning or can bring about the growth of dar hair in place of the grey or white hair.
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- Cosmetic composition
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A composition suitable for topical application to mammalian skin or hair for inducing, maintaining or increasing hair growth comprises a glycosaminoglycanase inhibitor chosen from aldonomonolactones, alduronomonolactones and acylated monosaccharides, and a cosmetically acceptable vehicle for the inhibitor; the total amount of the inhibitor present in the composition being sufficient to increase hair growth in the rat, when said composition is applied topically thereto over a period of no more than 3 months, by at least 10% more than that obtainable using a control composition from which the said inhibitor has been omitted, in accordance with the Rat Hair Growth Test.
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- Cosmestic composition
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A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamic acid derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.
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- Method of growing hair
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A method for inducing, maintaining or increasing hair growth which is achieved by topically applying a preserved composition to mammalian skin and hair in a mammal having need thereof, the composition comprising a hexosaccharic acid, salts and esters thereof, in an amount sufficient to induce, maintain or increase hair growth.
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- Hair growth composition containing citric acid esters
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Triesters of citric acid are used for inducing, maintaining or increasing hair growth. Compositions for topical application to mammalian hair or scalp comprise an effective amount of from 1% to 99% by weight of an ester of citric acid having the structure (1): where, R1, R2 and R3 each independently represent a branched or unbranched alkyl, alkenyl, aryl, alkylaryl or arylalkyl group, each said group having from 1 to 18 carbon atoms, R4 represents -H, or a branched or unbranched saturated or unsaturated acyl, alkyl, aryl, alkylaryl or aylalkyl group having from 1 to 18 carbon atoms, in the presence of a cosmetically acceptable vehicle for the citric acid ester and in the absence of solid absorbent for the ester;, said effective amount of said ester being sufficient to increase hair growth in the rat, when said composition is applied topically thereto over a period of no more than three months, by at least 10% more than that obtainable using a control composition from which the said ester has been omitted, in accordance with the Rat Hair Growth Test.
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- Cosmetic composition
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A composition suitable for topical application to mammalian skin or hair comprises: (a) a growth factor chosen from: (i) transforming growth factor alpha (TGF-α), (ii) transforming growth factor beta (TGF-β), (iii) insulin-like growth factor-1 (IGF-1), (iv) fragments thereof of one or more of said growth factors, and (v) mixtures thereof of said growth factors or fragments of said growth factors; and (b) a cosmetically acceptable vehicle for the growth factor or fragments thereof; the total amount of growth factor being sufficient to increase hair growth in the rate, when the composition is applies topically thereto over a period of no more than 3 months, by at least 10% more than that obtainable using a control composition from which the said growth factor has been omitted, in accordance with the Rat Hair Growth Test.
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- Lactams, their synthesis and use in cosmetic compositions
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A composition suitable for topical application to mammalian skin or hair for inducing, maintaining or increasing hair growth comprises: (i) a chemical inhibitor of glycosidase activity chosen from lactams having the structure: STR1 where A1 and A6 are --H, --CH3, STR2 --CH2 OT or STR3 A1 and A6 being the same or different, and at least one of which being the group: STR4 in a lactam ring; and where Q is --OT', --NHT' or a lactam linkage to A1 or A6 ; the Q groups being the same or different, and at least one of which is involved in a lactam linkage; and where T is the same or different and is chosen from --H, --Cp H2p+1 or a metal ion, T' is --H or --COCp H2p+1, and p is an integer of from 1 to 22; provided that: where any of the Q groups is --OT' or --NHT', then that group or groups can be of either stereochemical configuration with respect to the plane of the ring; and (ii) a cosmetically acceptable vehicle for the chemical inhibitor. Certain novel lactams are also claimed.
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- Carbohydrate lactam derivatives and their use in cosmetic compositions
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A composition suitable for topical application to mammalian skin or hair for inducing, maintaining or increasing hair growth comprises: (i) a chemical inhibitor of glycosidase activity chosen from lactams having the structure: where A1 and A6 are -H, -CH3,, - , or A1 and A6 being the same or different, and at least one of which being the group:, , , in a lactam ring;, and where Q is -OT?, -NHT? or a lactam linkage to A1 or A6;, the Q groups being the same or different, and at least one of which is involved in a lactam linkage;, and where T is the same or different and is chosen from, -H, -CpH2p+1or a metal ion,T? is -H or -COCpH2p+1, and, p is an integer of from 1 to 22;, provided that:, where any of the Q groups is, -OT? or -NHT?,then that group or groups can be of either stereochemical configuration with respect to the plane of the ring; and (ii) a cosmetically acceptable vehicle for the chemical inhibitor. Certain novel lactams are also claimed.
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