- A trisulfide-linked glycoprotein
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The first member of a novel class of chemoselective reagents, glycosyl methanedithiosulfonates, has been synthesized, identified and employed in the first examples of chemical, site-selective construction of a trisulfide-modified protein with complete conversion. The Royal Society of Chemistry.
- Bernardes, Goncalo J. L.,Marston, Justin P.,Batsanov, Andrei S.,Howard, Judith A. K.,Davis, Benjamin G.
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- Sodium thiosulfonate salts: Molecular and supramolecular structural features and solution radiolytic properties
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Three sodium thiosulfonate salts, NaMeS2O2· H2O, NaPhS2O2 and NaMeC6H 4S2O2 have been prepared by the direct reaction of the sodium sulfinate salts with elemental sulfur, a clean, benign route that produces no by-products. The structures of the phenyl (which crystallised as a hydrate, NaPhS2O2·1.5H2O) and p-tolyl compounds were determined by X-ray crystallography. For the p-tolyl derivative, NaMeC6H4S2O2, the unexpected coordination of the pendant sulfur atom was found, a feature not reported previously for thiosulfonate salts, and observed only in two of the more common thiosulfate salts. Intermolecular CH/π interactions are postulated to contribute to the driving force of sulfur coordination, otherwise a different orientation of the aromatic rings would be expected. For NaPhS2O 2·1.5H2O, the water ligands and thiosulfonate anions each contribute three oxygen atoms to form a NaO6 coordination sphere. The thiosulfonate and water oxygens bridge to other sodium atoms forming a three-dimensional layer structure consisting of sheets of NaPhS 2O2·1.5H2O with a hydrophilic interior layer, comprising the sodium ions, water ligands and -S2O 2- groups, and a hydrophobic exterior formed by the phenyl substituent. The structure is further stabilised by an extensive H-bonding network between the ligated water and the non-coordinating thiosulfonate sulfur atom forming part of the hydrophilic layer and by weak intermolecular edge-to-face CH/π interactions between the sheets. Investigation of the radical chemistry of the three salts using pulse radiolysis indicated that oxidation of NaMeS2O2·H2O involves formation of a sulfur-centred radical rather than hydrogen abstraction from the methyl substituent, whereas oxidation of the aromatic ring is the preferred pathway for the phenyl and p-tolyl derivatives.
- Fischmann, Adam J.,Spiccia, Leone
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experimental part
p. 12310 - 12319
(2012/01/31)
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- PROSTAGLANDIN PHARMACEUTICAL COMPOSITIONS
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The present invention relates to new prostaglandin derivatives having improved pharmacological activity and enhanced tolerability. They can be employed for the treatment of glaucoma and ocular hypertension.
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Page/Page column 4
(2010/07/08)
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- Coating Surfaces
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Disclosed is a method of attaching, indirectly, a member of a specific binding pair (or sbp) to a surface, the method comprising the steps of: (a) contacting the surface with a solution, preferably an aqueous solution, of a polymer, having side chains according to the formula X-Y-Z-R, wherein X is a spacer group; Y is a sulphur, selenium or tellurium atom; Z is a sulphur, selenium or tellurium atom, any of which may be bonded to one or two oxygen atoms; and wherein R is any suitable moiety such that -Z-R constitutes a leaving group; such that at least some of the -Z-R groups are displaced and the polymer becomes bound to the surface by X-Y groups; and (b) contacting a polymer-coated surface resulting from step (a) with a solution, preferably an aqueous solution, comprising an sbp member, so as to cause the polymer to react with the sbp member, so as to attach the sbp member, indirectly, to the surface.
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- Interactions of aromatic mannosyl disulfide derivatives with Concanavalin A: synthesis, thermodynamic and NMR spectroscopy studies
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α-d-Mannopyranosyl units were attached to an aromatic scaffold through disulfide linkages to obtain mono- to trivalent glycosylated ligands for lectin binding studies. Isothermal titration calorimetric (ITC) measurements indicated that binding affinities of these derivatives to Concanavalin A (Con A) were comparable to or slightly higher than that of methyl α-d-mannopyranoside (Ka values in the range of 104 M-1). The stoichiometries of the lectin-ligand complexes were in agreement with the formal valencies (1-3) of the respective ligands indicating cross-linking in interactions with the di- and trivalent derivatives. Multivalency effects could not, however, be observed with the latter. These ligands were shown to bind to the carbohydrate binding site of Con A using saturation transfer difference (STD) NMR competition experiments.
- Murthy, Bandaru Narasimha,Sinha, Sharmistha,Surolia, Avadhesha,Jayaraman, Narayanaswamy,Szilagyi, Laszlo,Szabo, Ildiko,Koever, Katalin E.
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experimental part
p. 1758 - 1763
(2009/12/24)
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- Efficient synthesis of methanesulphonate-derived lipid chains for attachment of proteins to lipid membranes
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We have developed an easy and flexible synthetic methodology to obtain lipid chains containing methanothiosulfonate terminal groups with the aim to attach them to natural proteins as functional groups. There are many proteins found in nature that are modified by lipids, and this is a key part of their function. For example, the prion protein is attached to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor, and this protein is thought to be the causative agent in diseases such as bovine spongiform encephalopathy (BSE; "mad cow disease") and the human equivalent Creutzfeldt-Jakob disease. However, production of large amounts of protein in bacteria results in proteins that lack these lipid modifications. The lipid chains containing methanothiosulfonate terminal groups that we have synthesized here can be attached to these proteins through the thiol contained in the side chain of the cysteine residue, which can be incorporated into the protein sequence at the desired position. Copyright Taylor & Francis Group, LLC.
- Hicks, Matthew R.,Rullay, Atvinder K.,Pedrido, Rosa,Crout, David H.,Pinheiro, Teresa J. T.
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p. 3726 - 3750
(2008/12/23)
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- Cardiovascular agents
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The present invention relates to novel compounds that are derivatives of angiotensin receptor blocker (ARB) that comprise in their formula a polysulfurated group and that are useful for treating cardio-vascular diseases, such as hypertension, ischemic heart disease, atherosclerosis, metabolic syndrome, etc. also in combination with other cardiovascular agents.
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Page/Page column 9-10
(2008/12/04)
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- 5-Fluorouracil derivatives and their use for the treatment of cancer
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The present invention relates to 5-fluoropyrimidine compounds of formula I that are useful for preventing, treating or reducing tumoral diseases and pathological conditions involving various cancer forms.
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Page/Page column 6
(2008/12/06)
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- PROSTAGLANDIN PHARMACEUTICAL COMPOSITIONS
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The present invention relates to new prostaglandin derivatives having improved pharmacological activity and enhanced tolerability. They can be employed for the treatment of glaucoma and ocular hypertension.
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Page/Page column 20-23
(2009/01/20)
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- Anti-inflammatory agents
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The present invention relates to novel thiosulfonates derivatives. The present invention also provides methods for preventing, treating and/or reducing inflammation-associated diseases in the cardiovascular, connective tissue, pulmonary, gastrointestinal, respiratory, urogenital, nervous or cutaneous systems as well as infective and tumoral diseases employing said compounds.
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Page/Page column 3-4
(2008/06/13)
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- SULINDAC DERIVATIVES FOR TREATMENT OF CANCER
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The present invention relates to novel non steroidal anti-inflammatory compounds (NSAIDs) derivatives of sulindac, for the treatment/prevention, alone or in combination, of cancer.
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Page/Page column 15-17
(2008/06/13)
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- SYNTHESIS AND USE OF GLYCODENDRIMER REAGENTS
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The present invention relates to a chemically modified mutant protein including a cysteine residue substituted for a residue other than cysteine n a precursor protein, the substituted cysteine residue being subsequently modified by reacting the cysteine residue with a glycosylated thiosulfonate. Also a method of producing the chemically modified mutant protein is provided. The present invention also relates to a glycosylated methanethiosulfonate. Another aspect of the present invention is a method of modifying the functional characteristics of a protein including providing a protein and reacting the protein with a glycosylated methanethiosulfonate reagent under conditions effective to produce a glycoprotein with altered functional characteristics as compared to the protein. In addition, the present invention relates to methods of determining the structure-function relationships of chemically modified mutant proteins. The present invention also relates to synthetic methods for producing thio-glycoses, the thio-glycoses so produced, and to methods for producing glycodendrimer reagents.
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Page/Page column 38; 39; sheet 23
(2010/11/08)
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- Glycosyl disulfides: Novel glycosylating reagents with flexible aglycon alteration
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Glycosyl disulfides have been shown for the first time to be effective glycosyl donors. Glucosylation and galactosylation of a panel of representative alcohol acceptors allowed the formation of 28 simple glycosides, disaccharides, and glycoamino acids in yields of up to 90%. As well as providing a novel class of effective glycosyl donors, the ability to easily alter the nature of the aglycon and the ability to differently activate donors that differ only in their aglycon simply through altering conditions lends glycosyl disulfide donors to their use in latent-active reactivity tuning strategies.
- Grayson, Elizabeth J.,Ward, Sarah J.,Hall, Alison L.,Rendle, Phillip M.,Gamblin, David P.,Batsanov, Andrei S.,Davis, Benjamin G.
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p. 9740 - 9754
(2007/10/03)
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- Chemically modified enzymes
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Modified enzymes are provided in which at least one amino acid, such as asparagine, leucine, methionine or serine, of an enzyme is replaced with a cysteine and the thiol hydrogen is replaced with a substituent group providing a thiol side chain selected from the group consisting of: a) —SR1R2, wherein R1is an alkyl and R2is a charged or polar moiety; b) —SR3, wherein R3is a substituted or unsubstituted phenyl; c) —SR4, wherein R4is substituted or unsubstituted cyclohexyl; d) —SR5, wherein R5is C10-C15alkyl; and e) —SR6wherein R6is a C1-6alkyl. Also, methods of producing the modified enzymes are provided, as well as detergent and feed additives and a composition for the treatment of a textile. A method for using the modified enzymes in organic synthesis is additionally provided. Further, modified enzymes having improved activity, altered pH profile and/or wash performance are provided.
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- Sulfinic Acids and Related Compounds. 19. Synthesis and Properties of 1-Propane-, 1-Butane-, and 1-Pentanesulfinates Terminally Substituted with Di- and Trisulfide Functions
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Preparation and reactions are compared, for n=3-5, of disulfide sulfinates with the structure RSS(CH2)nSO2Na (1) and of trisulfide bisalkanesulfinates with the structure 2S (5).The di- and trisulfides were prepared by reaction of cyclic thiosulfonates, and optimum preparations ot the thiosulfonates are considered.For 1, R was HO2CCH2CH2 (10-12), p-CH3C6H4 (13-15), C6H5 (16 and 17), 2,4,6-(CH3O)3C6H2 (n=4; 18), and H2N(CH2)2 (n=4; H in lieu of Na; 19).Several of the di- and trisulfides were sensitive to light (the trisulfides about equally).Much faster conversion for the disulfides occurred with heat for R = p-CH3C6H4 when n was 3 (13) or 4 (14) than when n was 5 (15); these results with 13-15 point as principal processes to homolysis with light but heterolysis with heat, the latter with operation of a neighboring-group effect of SO2Na on the SS bond.Sodium methanesulfinate readily forms a thiosulfonate with sulfur, and the implications of this reaction are developed for the chemistry of the trisulfide bissulfinates (5), where a novel rearrangement produces disulfide thiosulfonates (21, n=3-5).
- Macke, Jeffrey D.,Field, Lamar
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p. 396 - 402
(2007/10/02)
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- Benzopentathiepin as Sulfurization Reagent. Novel Synthesis of Thiosulfonates from Sulfinates
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Sodium alkane- and arenesulfinates were readily sulfurized with benzopentathiepin in usual organic solvents at room temperature to give corresponding thiosulfonates in good yields.
- Sato, Ryu,Akutsu, Yasuo,Goto, Takehiko,Saito, Minoru
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p. 2161 - 2162
(2007/10/02)
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