Abstract: The present invention provides new synthetic methods and compositions. In particular, new methods of preparing intermediates useful in the synthesis of neuraminidase inhibitors and compositions useful as intermediates that are themselves useful in the synthesis of neuraminidase inhibitors are provided.

Abstract: Novel carbocyclic compounds are described. The compounds generally comprise an acidic group, a basic group, a substituted amino or N-acyl and a group having an optionally hydroxylated alkane moiety. Pharmaceutical compositions comprising the inhibitors of the invention are also described. Methods of inhibiting neuraminidase in samples suspected of containing neuraminidase are also described. Antigenic materials, polymers, antibodies, conjugates of the compounds of the invention with labels, and assay methods for detecting neuraminidase activity are also described.

Abstract: The present invention provides new synthetic methods and compositions. In particular, new methods of preparing intermediates useful in the synthesis of neuraminidase inhibitors and compositions useful as intermediates that are themselves useful in the synthesis of neuraminidase inhibitors are provided.

Abstract: Oligonucleotide sequences that mediate specific binding to selected target molecules and contain modified base, sugars, or sugar linkages are disclosed. Single-stranded DNA oligomers are obtained that bind to a series of biomolecules that differ in both size and composition. The range of target molecules that may be bound permits generation of binding oligomers that are specific for binding to nearly any biomolecule that is composed of amino acids, lipids and/or carbohydrates. The binding oligomers are useful for therapeutic, diagnostic and manufacturing purposes.

Abstract: Tri- and tetra substituted thiepane compositions having use as immunogens, therapeutics, diagnostics and for other industrial purposes are disclosed. The compositions inhibit proteolytic activity of viral enzymes and are useful for the inhibition of such enzymes as well as in assays for the detection of such enzymes. Embodiments in which antigenic polypeptides are bonded to the compositions are useful in raising antibodies against the thiepane haptens or the polypeptide. Labeled thiepanes of this invention are useful as diagnostic reagents.

Abstract: Novel carbocyclic compounds are described. The compounds generally comprise an acidic group, a basic group, a substituted amino or N-acyl and a group having an optionally hydroxylated alkane moiety. Pharmaceutical compositions comprising the inhibitors of the invention are also described. Methods of inhibiting neuraminidase in samples suspected of containing neuraminidase are also described. Antigenic materials, polymers, antibodies, conjugates of the compounds of the invention with labels, and assay methods for detecting neuraminidase activity are also described.

Abstract: A method for identifying oligomer sequences, optionally comprising modified base, which specifically bind target molecules such as serum proteins, kinins, eicosanoids and extracellular proteins is described. The method is used to generate aptamers that bind to serum Factor X, PDGF, FGF, ICAM, VCAM, E-selectin, thrombin, bradykinin, PGF2 and cell surface molecules. The technique involves complexation of the target molecule with a mixture of oligonucleotides containing random sequences and sequences which serve as primer for PCR under conditions wherein a complex is formed with the specifically binding sequences, but not with the other members of the oligonucleotide mixture. The complex is then separated from uncomplexed oligonucleotides and the complexed members of the oligonucleotide mixture are recovered from the separated complex using the polymerase chain reaction.

Abstract: A compound of the Formula I or Formula II ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen, hydroxy, chlorine, fluorine, bromine, or an organic substituent having 1 to 5 carbon atoms and selected from acyloxy having a hydrocarbon stem of 1 to 4 carbon atoms, alkoxy, alkylthio, amino, alkylamino and dialkylamino;R.sup.3 and R.sup.4 are independently hydrogen, or organic phosphonic ester substituents having 1 to 12 carbon atoms and selected from alkyl, alkenyl, aryl, and aralkyl; andB is a heterocyclic group selected from the group consisting of pyrimidine, purine, triazine, deazapurine, and triazole, attached through a ring nitrogen atom thereof optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, mercapto, amino, hydrazino, fluoro, chloro, bromo, iodo, C.sub.1 to C.sub.3 alkyl, C2-C3 alkenyl, C2-C3 haloalkenyl, C1-C3 alkoxy, and C1-C3 alkylthio;and the pharmaceutically acceptable acid addition, metal, and amine salts thereof.

Abstract: Tri- and tetra substituted thiepane and compositions having use as immunogens, therapeutics, diagnostics and for other industrial purposes are disclosed. The compositions inhibit proteolytic activity of viral enzymes and are useful for the inhibition of such enzymes as well as in assays for the detection of such enzymes. Embodiments in which antigenic polypeptides are bonded to the compositions are useful in raising antibodies against the thiepane haptens or the polypeptide. Labeled thiepanes of this invention are useful as diagnostic reagents.

Abstract: Novel hydrogen-phosphonodithioate compositions are provided which are particularly useful for forming internucleotide and internucleoside linkages in oligonucleosides or oligonucleotides, The oligonucleotides and analogs thereof made by using the hydrogen-phosphonodithioate compositions may be therapeutically useful as antiviral and anticancer agents and may have other therapeutic or diagnostic uses, A method for making the hydrogen-phosphonodithioates is provided as well as a method for converting same to an activated intermediate for substitution on the phosphorus atom.

Abstract: Methods and compositions are disclosed for determining a peroxidatively active catalyst. The methods comprise the step of detecting a substance formed by the coupling reaction of (a) the product of the peroxidatively active catalyst-catalyzed oxidation of a benzidine with (b) a coupler other than benzidine. The methods have application in a wide variety of systems including assays for analytes. Also disclosed are kits for conducting methods and assays in accordance with the present invention.

Abstract: Oligonucleotides having tandem sequences of inverted polarity, i.e., oligonucleotides comprising regions of the formula: ##STR1## wherein --C-- symbolizes any method of coupling the nucleotide sequence of opposite polarity, are useful for forming an extended triple helix with a double-helical nucleotide duplex. The inverted polarity also stabilizes the single-strand oligonucleotides to exonuclease degradation.

Abstract: A kit is disclosed for a method for detecting the presence of a target polynucleotide sequence. The kit comprises a first polynucleotide sequence and a second polynucleotide sequence complementary to non-contiguous portions of a target polynucleotide sequence, which first and second sequences are covalently attached when they are hybridized to the target sequence. The presence of the covalently attached first and second sequences is related to the presence of the target polynucleotide sequence. The invention may be applied to target polynucleotide sequences in DNA or RNA. Specific target polynucleotide sequences of interest will frequently be characteristic of particular microorganisms, viruses, viroids, or genetic characteristics, including genetic abnormalities.

Abstract: A composition comprising a compound of the formula: ##STR1## wherein: X is H or OH;Y is a group capable of hydrogen bonding to amino, guanidino, or imidazole function, or a group comprising an acidic hydrogen atom, a protected acidic group, or an anion;E is N or CR.sub.1, wherein R.sub.1 is H, OH, CN, F, Cl, Br, or I;A.sub.4, A.sub.5, and A.sub.6 are each independently N, CH, CR.sub.40 or CZ wherein R.sub.40 is R.sub.43, OR.sub.43, SR.sub.43, S(O)R.sub.43, S(O).sub.2 R.sub.43, or NR.sub.43 R.sub.44 wherein R.sub.43 comprises an alkyl of 1 to 3 carbon atoms, an acyl of 2 to 3 carbon atoms, or an alkyl of 1 to 3 carbon atoms substituted with an acyl of 2 to 3 carbon atoms, and R.sub.44 is H or an alkyl of 1 to 2 carbon atoms, and Z is a group capable of hydrogen bonding to carboxyl, or a group comprising a basic heteroatom, a protected basic heteroatom, or a cation.

Abstract: Methods and compositions are disclosed for determining a peroxidatively active substance (PAS). The methods comprise the step of detecting a fluorescent signal produced upon cleavage of a compound of the formula F-L-Q, wherein F is a fluorescer capable of producing the signal, Q is a quencher capable of quenching the signal when linked to F, and L is a bond, or a linking group having a bond, wherein the bond is capable of being cleaved by a reaction of the PAS with a substrate of the PAS and a hydrogen donor wherein the cleavage of the bond substantially reduces the quenching. The methods have application in a wide variety of systems including assays and improved assays for analytes. Also disclosed are kits for conducting the methods and improvements in accordance with the present invention.

Abstract: Compounds and methods are disclosed for reversibly aggregating particles suspended in a liquid medium. The method comprises combining the liquid medium containing the particles with a polyionic polymer capable of aggregating the particles under conditions suitable for such aggregation. Thereafter, the particles are contacted with a chemical reagent capable of cleaving the polyionic polymer under conditions sufficient to reverse the aggregation. Optionally, magnetic particles are added to the liquid medium in the present method under conditions for non-specific binding and the medium including the aggregates is subjected to a magnetic field gradient to separate the aggregates from the medium. The compounds of the present invention are polyions. The aggregation of the particles is reversible upon contact with chemical agents which cleave at least some of the bonds within the polyionic polymer.

Abstract: Methods and compositions are disclosed for determining a peroxidatively active substance (PAS). The methods comprise the step of detecting a fluorescent signal produced upon cleavage of a compound of the formula F-L-Q, wherein F is a fluorester capable of producing the signal, Q is a quencher capable of quenching the signal when linked to F, and L is a bond, or a linking group having a bond, wherein the bond is capable of being cleaved by a reaction of the PAS with a substrate of the PAS and a hydrogen donor wherein the cleavage of the bond substantially reduces the quenching. The methods have application in a wide variety of systems including assays and improved assays for analytes. Also disclosed are kits for conducting the methods and improvements in accordance with the present invention.

Abstract: Novel squaraine dyes and compositions of matter containing such dyes are disclosed . The novel squaraine dyes have an absorption maximum greater than 600 nanometers and are particularly useful in conjunction with a helium/neon (He/Ne) laser. Some of the squaraine dyes are hydrophilic and are therefore water soluble or water compatible and others of the squaraine dyes are lipophilic.

Abstract: An evaporation closure is disclosed. One embodiment of the closure includes a cap, made of pliable material, which in turn includes a top wall having an opening, a skirt downwardly depending from the top wall and having a threadless internal wall adapted to slip on and sealingly engage a container, and biasing means integral with the skirt; and an elongated arm, which in turn includes a means for sealing the opening, pivotally attached to the cap for movement between a first position wherein the sealing means seals the opening and a second position wherein the sealing means does not seal the opening, the arm being biased toward the first position by the biasing means. Such a closure is useful for minimizing evaporation from containers, particularly automated clinical analyzer reagent bottles.A kit including in packaged combination component parts of the evaporation closure is also disclosed. Such a kit is useful for conveniently assembling the evaporation closures of the present invention.

Abstract: Methods are disclosed for separating a component of interest from a mixture containing the component of interest and other components. The method comprises contacting a first liquid medium containing the component of interest and other components with a second liquid medium that is of different density than and/or of different viscosity than the first liquid medium. The contact is carried out in such a way that mixing of the media is minimized or avoided. The component of interest is bound to magnetic particles. The contacted first liquid medium and second liquid medium are subjected to a magnetic field gradient to allow the magnetic particles to migrate into the second liquid medium and separation of the component of interest from other components is realized. Also disclosed are assays employing the present method. Kits for carrying out the present method and assays are also disclosed.