Abstract: The transition state structure of thymidine phosphorylase is provided, along with thymidine phosphorylase inhibitors that resemble the charge and geometry of the thymidine phosphorylase transition state. Also provided are methods of inhibiting a thymidine phosphorylase, methods of treating cancer, and methods of inhibiting angiogenesis which utilize the thymidine phosphorylase transition state inhibitors.

Abstract: Improved transition state analog inhibitors of ricin toxin-A are provided. Methods of using those inhibitors to inhibit ricin toxin-A and to prevent the toxic effects of rich toxin-A in a mammal are also provided.

Abstract: The present invention relates to methods for integrated ribonucleic acid integrity assessment and analysis comprising the steps of: (a) providing a support having immobilized thereon a set of detector probes and a set of at least two control probes, wherein (i) a first of said at least two control probes is complementary to 23S or 28S rRNA or a functionally equivalent RNA, and (ii) a second of said at least two control probes is complementary to 16S or 18S10 rRNA or a functionally equivalent RNA; (b) contacting said support with analyte ribonucleic acids derived from a sample, under conditions allowing hybridisation of complementary analyte ribonucleic acids and immobilized probes to form analyte ribonucleic acid/probe complexes; wherein said hybridisation generates a detectable signal; 15 (c) detecting signals generated by said complexes; (d) determining the ratio of signals generated by the 28S/control probe and 18S rRNA/control probe or 23S rRNA/control probe and 16S rRNA/control probe or functionally equi

Abstract: The present invention provides compounds having the formula: wherein A is CH or N; B is chosen from OH, NH2, NHR, H or halogen; D is chosen from OH, NH2, NHR, H, halogen or SCH3; R is an optionally substituted alkyl, aralkyl or aryl group; and X and Y are independently selected from H, OH or halogen except that when one of X and Y is hydroxy or halogen, the other is hydrogen; and Z is OH or, when X is hydroxy, Z is selected from hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof; and compounds having the formula: wherein A, X, Y, Z and R are defined for compounds of formula (I) where first shown above; E is chosen from CO2H or a corresponding salt form, CO2R, CN, CONH2, CONHR or CONR2; and G is chosen from NH2, NHCOR, NHCONHR or NHCSNHR; or a tautomer thereof, or a pharmaceutically acceptable salt thereof, or an ester thereof, or a prodrug the

Abstract: A process of preparing a compound of the formula (I) wherein B is chosen from OH, NH2, NHR, H or halogen; D is chosen from OH, NH2, NHR, H halogen or SCH3; R is an optionally substituted alkyl, aralkyl or aryl group; and Z is selected from OH, hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof, which comprises reacting a compound of the formula (II) with an anion produced by abstraction of the bromine or iodine atom from a compound of formula (XIX),

Abstract: The present invention provides a compound of formula (I), wherein: A is selected from N, CH and CR, where R is selected from halogen, optionally substituted alkyl, aralkyl and aryl, OH, NH2, NHR1, NR1R2 and SR3, where R1, R2 and R3 are each optionally substituted alkyl, aralkyl or aryl groups; B is selected from OH, NH2, NHR4, H and halogen, where R4 is an optionally substituted alkyl, aralkyl or aryl group; D is selected from OH, NH2, NHR5, H, halogen and SCH3, where R5 is an optionally substituted alkyl, aralkyl or aryl group; X and Y are independently selected from H, OH and halogen, with the proviso that when one of X and Y is hydroxy or halogen, the other is hydrogen; Z is OH, or, when X is hydroxy, Z is selected from hydrogen, halogen, hydroxy, SQ and OQ, where Q is an optionally substituted alkyl, aralkyl or aryl group; and W is OH or H, with the proviso that when W is OH, then A is CR where R is as defined above; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof

Abstract: The present invention relates to compounds of the general formula (I) which are inhibitors of purine muclioside phosphorylases (PNP), purine phosphoribosyltransferases (PPRT), 5?-methylthioadenosine phosphorylases (MTAP), 5?-methylthioadenosine mucliosidases (MTAN) and/or nucleoside hydrolases (NH). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

Abstract: The present invention provides compounds having the formula: wherein A is a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group, the group being further substituted with an electron contributing moiety; B is hydrogen, or a halogen, amino, or thiol group; C is hydrogen, or a halogen, amino, or thiol group; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.

Abstract: A process of preparing a compound of the formula (I) wherein B is chosen from OH, NH2, NHR, H or halogen; D is chosen from OH, NH2, NHR, H halogen or SCH3; R is an optionally substituted alkyl, aralkyl or aryl group; and Z is selected from OH, hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof, which comprises reacting a compound of the formula (II) with an anion produced by abstraction of the bromine or iodine atom from a compound of formula (XIX), to form a compound of formula (XX) The compound of formula (XX) is N- and O-deprotected to obtain the compound of formula (I).

Abstract: The present invention provides compounds having the formula: (I); Also provided are pro-drug compounds of the formula: (II); The invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds. Methods for inhibiting an ADP-ribosyl transferase, ADP-ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme using the above compounds, and methods for treating a disease or condition associated with an ADP-ribosyl transferase, ADP-‘ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme in a subject using the above compounds are also provided.

Abstract: The present invention provides compounds having the formula: wherein A is chosen from a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group; both B and C are hydrogen, or either B or C is a halogen, amino, or thiol group and the other of B or C is hydrogen; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds.

Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: The present invention provides compounds having the formula: wherein A is CH or N; B is chosen from OH, NH2, NHR, H or halogen; D is chosen from OH, NH2, NHR, H, halogen or SCH3; R is an optionally substituted alkyl, aralkyl or aryl group; and X and Y are independently selected from H, OH or halogen except that when one of X and Y is hydroxy or halogen, the other is hydrogen; and Z is OH or, when X is hydroxy, Z is selected from hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof; and compounds having the formula: wherein A, X, Y, Z and R are defined for compounds of formula (I) where first shown above; E is chosen from CO2H or a corresponding salt form, CO2R, CN, CONH2, CONHR or CONR2; and G is chosen from NH2, NHCOR, NHCONHR or NHCSNHR; or a tautomer thereof, or a pharmaceutically acceptable salt thereof, or an ester thereof, or a prodrug the