Abstract: A practical method for enzymatically synthesizing c-di-GMP with excellent productivity is provided. A diguanylate cyclase having physical and chemical characteristics (A) to (F): (A) catalytic action on reaction “2 GTP?c-di-GMP”; (B) a molecular weight of 19800±2000; (C) an optimum pH of 7.3 to 9.4; (D) an optimum temperature of 35 to 60° C.; (E) thermal stability as the remaining activity of 90% or higher after heated for 60 minutes under conditions of 50° C. and pH7.8; and (F) the presence of GGDEF (SEQ ID NO:26) domain and the lack of amino acid sequence KXXD (SEQ ID NO:23) in the i-site.

Abstract: Water-forming NADH oxidase derived from Streptococcus mutans should be further improved in terms of stability for practical use in industrial production. An object of the present invention is to provide an enzyme that is obtained through modification of a water-forming NADH oxidase, which is useful as an NAD+ regeneration system for stereoselective oxidation catalyzed by an oxidoreductase, by protein engineering techniques so that the enzyme can withstand long-term use without exhibiting a reduction of its activity for the regeneration of NAD+, that is, an enzyme having improved stability, and to provide a method for efficiently producing a useful substance such as an optically active alcohol or amino acid. The present invention relates to an enzyme modification method that can improve the stability of water-forming NADH oxidase derived from Streptococcus mutans by appropriately introducing mutation.

Abstract: A method for rapidly measuring melatonin adulteration of Chinese patent medicines and healthcare foods comprises: (1) extracting melatonin added to a Chinese patent medicine or healthcare food by using ethyl acetate; and (2) adding p-dimethylaminocinnamaldehyde to the extracted solution, and observing color. The method is rapid, simple and convenient, has strong specificity, high accuracy, reaction sensitivity, and a wide application range, and is applicable to on-site detection of melatonin adulteration of a Chinese patent medicine or healthcare food.

Abstract: A practical method for enzymatically synthesizing c-di-GMP with excellent productivity is provided. A diguanylate cyclase having physical and chemical characteristics (A) to (F): (A) catalytic action on reaction “2 GTP?c-di-GMP”; (B) a molecular weight of 19800±2000; (C) an optimum pH of 7.3 to 9.4; (D) an optimum temperature of 35 to 60° C.; (E) thermal stability as the remaining activity of 90% or higher after heated for 60 minutes under conditions of 50° C. and pH 7.8; and (F) the presence of GGDEF domain and the lack of amino acid sequence KXXD in the i-site.

Abstract: The present invention relates to cofactor regeneration systems, components and uses thereof and methods for generating and regenerating cofactors. The cofactor regeneration system comprises a first electron transfer component selected from a polypeptide comprising a NADH:acceptor oxido-reductase or NADPH:acceptor oxido-reductase, a second electron transfer component selected from a hydrogenase moiety and/or non-biological nanoparticles and an electronically conducting surface. The first and second electron transfer components are immobilised on the electrically conducting surface, and the first and second electron transfer components do not occur together in nature as an enzyme complex.

Abstract: A process for the enzymatic regeneration of the redox cofactors NAD+/NADH and NADP+/NADPH in a one-pot reaction, wherein, as a result of at least two further enzymatically catalyzed redox reactions proceeding in the same reaction batch (product-forming reactions), one of the two redox cofactors accumulates in its reduced form and, respectively, the other one in its oxidized form, characterized in that a) in the regeneration reaction which reconverts the reduced cofactor into its original oxidized form, oxygen or a compound of general formula R1C(O)COOH is reduced, and b) in the regeneration reaction which reconverts the oxidized cofactor into its original reduced form, a compound of general formula R2CH(OH)R3 is oxidized and wherein R1, R2 and R3 in the compounds have different meanings.

Abstract: Described is a new stand-alone diguanylate cyclase polypeptide having a GGDEF motif and a mutated I-site that does not bind c-di-GMP. We demonstrate that the production yield of c-di-GMP and analogues was significantly increased by mutation of a conserved residue in the putative regulatory I-site.

Abstract: An object of the present invention is to provide a method for converting the coenzyme dependency of enzymes of the medium-chain dehydrogenase/reductase (MDR) family. A further object of the present invention is to provide enzyme variants of the MDR family whose coenzyme dependency is converted by the conversion method and a method for enzymatically producing optically active alcohols using the enzymes. The present inventors developed a novel enzyme conversion method for converting the coenzyme dependency of enzymes of the MDR family, rationally designed enzyme variants that are altered by the enzyme conversion method to be able to use NADPH as a coenzyme from a useful enzyme of the MDR family that uses NADH as a coenzyme, and actually provide variants having such an ability.

Abstract: The present invention provides a recombinant polypeptide comprising a first portion and a second portion, wherein the sequence of the first portion is fully identical to amino acids 1 to 248 of the sequence set forth as SEQ ID NO:1 and the sequence of the second portion is other than amino acids 249 to 511 of the sequence set forth as SEQ ID NO:1.

Abstract: The invention relates to a nucleic acid molecule comprising a section that encodes a signal peptide, a section that comprises a heterologous redox factor-regenerating polypeptide, an optional section that encodes a protease detection site, a section that encodes a transmembrane linker, and a section that encodes a transporter domain of an autotransporter or a variant thereof. The nucleic acid molecule enables the expression of redox factor-regenerating enzymes.

Abstract: The invention relates to a glucose dehydrogenase showing an NADP/NAD activity ratio, namely the value obtained by dividing the enzyme activity value obtained by using NADP as a coenzyme by the enzyme activity value obtained by using NAD as a coenzyme, of not lower than 300, to a gene coding therefor, and to a transformant harboring that gene. The enzyme of the invention is very high in NADP specificity and can be suitably used, for example, for NADPH production, for coenzyme regeneration in enzymatic reduction reactions, and in biosensors for glucose concentration measurements.

Abstract: Water-forming NADH oxidase derived from Streptococcus mutans should be further improved in terms of stability for practical use in industrial production. An object of the present invention is to provide an enzyme that is obtained through modification of a water-forming NADH oxidase, which is useful as an NAD+ regeneration system for stereoselective oxidation catalyzed by an oxidoreductase, by protein engineering techniques so that the enzyme can withstand long-term use without exhibiting a reduction of its activity for the regeneration of NAD+, that is, an enzyme having improved stability, and to provide a method for efficiently producing a useful substance such as an optically active alcohol or amino acid. The present invention relates to an enzyme modification method that can improve the stability of water-forming NADH oxidase derived from Streptococcus mutans by appropriately introducing mutation.

Abstract: The invention provides an isolated formate dehydrogenase (FDH) polypeptide specific for NADP+ and an isolated FDH polypeptide having an adenine ribose recognition loop comprising a first large amino acid and a second amino acid, wherein the first and second amino acid are arranged in space to allow the second amino acid to bond with a phosphate group. Also provided is a variant of an BAD+ specific FDH polypeptide, wherein the adenine ribose recognition loop has been mutated at least one position to alter the three dimensional polypeptide structure of the adenine ribose recognition loop to allow a phosphate group to be recognised. The polypeptides of the invention can be used in the conversion of NADP+ to NADP or in the conversion of BAD+ to NASH.

Abstract: The present invention generally relates to a nicotinamide adenine dinucleotide (NAD) biosynthesis system and methods of screening for NAD biosynthesis effectors. Among the various aspects of the present invention is the provision of an in vitro-reconstituted mammalian NAD biosynthesis system that can be used for the high-throughput screening of chemical activators and inhibitors for mammalian NAD biosynthesis. Another aspect of the invention provides a method of identifying a compound that effects in vivo activity of NAD metabolic enzymes. Further aspects of the invention include nucleic acid sequences, vectors, and transformed cells that can be used in the methods described herein.

Abstract: The present invention relates to a process for the production of a polyamine involving the use of enzymes; in particular to a process performed in aqueous environment; to the polyamines produced by said method; as well as the use of said polyamines for manufacturing paper, for immobilizing enzymes, or for preparing pharmaceutical or cosmetical compositions. The invention also relates to a novel method for in situ regeneration of cofactors NAD(P)+.

Abstract: A process for the enantioselective reduction of compounds having a steroid structure (ABCD) including one or several heteroatoms, one or several double bonds and/or aromatic components in the ring structure and having at least one oxo group at positions 3, 7, 11, 12 or 17 in the steroid ring system or in the a-position of any carbon moiety of the steroid structure: comprising providing the oxosteroid compound in the reaction at a concentration of ?50 g/L, a reduced cofactor NADH or NADPH, a hydroxysteroid dehydrogenase and a secondary alcohol or cycloalknaol to effect the enantioselective reduction.

Abstract: A method is described for producing an L-amino acid or a nucleic acid by culturing a microorganism having an ability to produce the L-amino acid or nucleic acid in a liquid medium in a fermentation tank containing a stirring impeller, and optionally adding seed crystals to the medium as required to produce and accumulate crystals of the L-amino acid or nucleic acid in the medium, and collecting crystals of the L-amino acid or nucleic acid from the culture. The power density of the stirring impeller is controlled to be 2.4 kW/m3 or lower after either precipitation of the crystals or addition of the seed crystals.

Abstract: Described is a new stand-alone diguanylate cyclase polypeptide having a GGDEF motif and a mutated I-site that does not bind c-di-GMP. We demonstrate that the production yield of c-di-GMP and analogues was significantly increased by mutation of a conserved residue in the putative regulatory I-site.

Abstract: A process is disclosed for the production of cyclic di-guanosine monophosphate (c-di-GMP) without the use of protecting groups by means of an enzymatic synthesis. The process comprises the coupling of two guanosine triphosphate (GTP) molecules so as to form a c-di-GMP molecule. This is done under the influence of a mutant diguanylate cyclase (DGC) comprising the amino acid sequence V153M154G155G156. It has been found that the DGC is obtainable from inclusion bodies, and therewith can be made available in amounts sufficient to improve the c-di-GMP synthesis. Particularly, the latter synthesis can be conducted in a one-pot method starting from commercially available bulk chemicals and allows upscaling to a commercial production scale.

Abstract: The present invention relates to the use of oxidized nicotinamide adenine dinucleotide (NAD+) or of its reduced form, NADH, as sodium channel modulators. The present invention also relates to the use of compositions containing NAD+ or NADH to treat conditions associated with sodium channel current, such as arrhythmia. NAD+ is found to increase sodium channel current, while NADH is found to decrease sodium channel current. Thus, conditions that are associated with decreased sodium channel current can be treated with NAD+, while conditions that is associated with increased sodium channel current can be treated with NADH.

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: Phosphite dehydrogenase mutant enzymes provide relaxed cofactor specificity, increased thermostability, increased activity, solubility, and expression over the wild-type enzyme. The mutant enzymes are useful for nicotinamide cofactor regeneration.

Abstract: The present invention generally relates to a nicotinamide adenine dinucleotide (NAD) biosynthesis system and methods of screening for NAD biosynthesis effectors. Among the various aspects of the present invention is the provision of an in vitro-reconstituted mammalian NAD biosynthesis system that can be used for the high-throughput screening of chemical activators and inhibitors for mammalian NAD biosynthesis. Another aspect of the invention provides a method of identifying a compound that effects in vivo activity of NAD metabolic enzymes. Further aspects of the invention include nucleic acid sequences, vectors, and transformed cells that can be used in the methods described herein.

Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.

Abstract: The present invention is directed to a new NADH oxidase from Lactobacillus, nucleic acids encoding the NADH oxidase, methods of producing the NADH oxidase, as well as there use in producing improved NADH oxidase enzymes and for producing chrial enantiomer-enriched organic compounds, such as alcohols and/or amino acids.

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: A fluid processing device and method of using the device are provided. The fluid processing device can include a substrate with a fluid processing pathway at least partially formed in or on the substrate. The fluid processing pathway can include an input end, at least one output end, a first input opening, a plurality of reaction sites each in fluid communication with the first input opening and arranged between the first input opening and the at least one output end. The fluid processing pathway can include a plurality of second input openings including two or more in fluid communication respectively with each of the reaction sites, the second input openings being arranged with the reaction site disposed between the at least one output end and the second input openings. The fluid processing device can include one or more output openings in fluid communication with one or more of the plurality of reaction sites and arranged at the at least one output end of the fluid processing pathway.

Abstract: An isolated nucleic acid comprising the nucleotide sequence of SEQ ID NO:1, or the full complementary sequence thereof. Presence of said nucleic acid in a subject predisposes the subject to an adenocarcinoma. Also disclosed are a method of diagnosing an adenocarcinoma.

Abstract: The ability to synthesize capped RNA transcripts in vitro has been of considerable value in a variety of applications. However, one-third to one-half of the caps have, until now, been incorporated in the reverse orientation. Such reverse caps impair the translation of in vitro-synthesized mRNAs. Novel cap analogues, such as P1-3?-deoxy-7-methylguanosine-5?P3-guanosine-5?triphosphate and P1-3?-O,7-dimethylguanosine-5?P3-guanosine-5?triphosphate, have been designed that are incapable of being incorporated into RNA in the reverse orientation. Transcripts produced with SP6 polymerase using “anti-reverse” cap analogues were of the predicted length. Analysis of the transcripts indicated that reverse caps were not formed. The in vitro translational efficiency of transcripts with the novel “anti-reverse” cap analogues was significantly higher than that of transcripts formed with conventional caps.

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 is directed to nucleoside monomers wherein the 3?-O atom is replaced with a methylene group. The present invention also provides oligomers comprising a plurality of such monomers which are linked by methylene phosphonate linkages. Further, methods of preparing monomers and oligomers according to the present invention are provided.

Abstract: A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled elektrokinetic assembly of particles near surfaces relies on the combination of three functional elements, the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.

Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.

Abstract: Therapeutic oligonucleotide analogues which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligomers with four atom linking groups forms unique di- and poly-nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

Abstract: A ferromagnetic thin-film based magnetic field detection system used for detecting the presence of selected molecular species. A magnetic field sensor supported on a substrate has a binding molecule layer positioned on a side thereof capable of selectively binding to the selected molecular species. The magnetic field sensor can be substantially covered by an electrical insulating layer having a recess therein adjacent to the sensor in which the binding molecule layer is provided. An electrical interconnection conductor can be supported on the substrate at least in part between the sensor and the substrate, and is electrically connected to the sensor. The magnetic field sensor can be provided in a bridge circuit, and can be formed by a number of interconnected individual sensors. A polymeric channel and reservoir structure base is provided for the system.

Abstract: An objective of the present invention is to provide polypeptides capable of retaining a strong enzyme activity of formate dehydrogenase in the presence of an organic solvent and to provide the uses thereof. Formate dehydrogenase mutant polypeptides, which are resistant to organic solvents, were constructed by substituting cysteines at position 146 and/or at position 256 in the amino acid sequence of Mycobacterium vaccae-derived formate dehydrogenase by site-directed mutagenesis. The polypeptides have strong activities of formate dehydrogenase in the presence of an organic solvent. The mutants are useful for the production of alcohols using ketones as raw material, etc.

Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.

Abstract: The present invention is directed to use of hyperthermophilic enzymes for industrial chemical redox reactions such as ethanol production. The present invention is especially useful for the coupled synthesis and recovery of alcohols whereby recovery of alcohol is simplified.

Abstract: The present invention describes a novel recombinant NADH recycling system that is used as a process for producing reduced compounds. In a specific embodiment, the reduced compounds include ethanol, succinate, lactate, a vitamin, a pharmaceutical and a biodegraded organic molecule. The NADH recycling system effects metabolic flux of reductive pathways in aerobic and anaerobic environments.

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 methods and devices for detecting a target nucleic acid molecule. A set of oligonucleotide probes integrated into an electric circuit, where the oligonucleotide probes are positioned such that they can not come into contact with one another, are contacted with a sample. If the sample contains a target nucleic acid molecule, one which has sequences complimentary to both probes, the target nucleic acid molecule can bridge the gap between the probes. The resulting bridge can then carry electrical current between the two probes, indicating the presence of the target nucleic acid molecule.

Abstract: A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.

Abstract: Propargylethoxyamino nucleosides are disclosed having the structure wherein R1 and R2 are —H, lower alkyl, or label; B is a 7-deazapurine, purine, or pyrimidine nucleoside base; W1 is —H or —OH; W2 is —OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3′-position; and W3 is —PO4, —P2O7, —P3O10, phosphate analog, or —OH. Additionally, a primer extension method is provided employing the above propargylethoxyamino nucleosides.

Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.

Abstract: The present invention provides methods and devices for detecting a target nucleic acid molecule. A set of oligonucleotide probes integrated into an electric circuit, where the oligonucleotide probes are positioned such that they can not come into contact with one another, are contacted with a sample. If the sample contains a target nucleic acid molecule, one which has sequences complimentary to both probes, the target nucleic acid molecule can bridge the gap between the probes. The resulting bridge can then carry electrical current between the two probes, indicating the presence of the target nucleic acid molecule.

Abstract: A method and apparatus for the manipulation of colloidal particles and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.

Abstract: Propargylethoxyamino nucleosides are disclosed having the structure wherein R1 and R2 are —H, lower alkyl, or label; B is a 7-deazapurine, purine, or pyrimidine nucleoside base; W1 is —H or —OH; W2 is —OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3′-position; and W3 is —PO4, —P2O7, —P3O10, phosphate analog, or —OH. Additionaly, a primer extension method is provided employing the above propargylethoxyamino nucleosides.

Abstract: The invention relates to new mutants of formate dehydrogenase from Candida boidinii, new gene sequences encoding these and use of the new formate dehydrogenases. The wild type FDH used hitherto in the industrial process for preparing amino acids becomes inactive after a certain time. New mutants of this wild type have been produced by targeted mutagenesis of a recombinant FDH from E. coli. The new mutants are preferably used in an enzymatic process for preparing chiral compounds.

Abstract: A molecular sensing apparatus comprises a first electrode (10), a second electrode (12), a first molecule (20), a second molecule (22), and a third molecule (34). The first molecule (20) has a first chain of nucleic bases (30) and a first group (24). The first group (24) is bound to the first electrode (10). The second molecule (22) has a second chain of nucleic bases (32) and a second group (26). The second group (26) is bound to the second electrode (12). The third molecule (34) is bound to the first molecule (20) and the second molecule (22). A method which uses the molecular sensing apparatus is disclosed.

Abstract: Compounds having structure (1) ##STR1## wherein R.sup.1 is --H a protecting group, a linker or a binding partner; and R.sup.2 and R.sup.34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.