Abstract: An oligonucleotide is synthesized by adding a 3'-phosphate blocked nucleotide to a primer, removing the blocking group from the primer-blocked nucleotide product using a thermostable 3'-phosphatase enzyme, and repeating these steps until the desired nucleotides have been added to the primer. A suitable phosphatase enzyme for use in this method is a thermostable phosphatase derived from the hyperthermophilic archaebacterium Pyrococcus furiosus.

Abstract: Novel .beta.-lactam monomers bearing various functional groups are prepared. The novel .beta.-lactam monomers can be joined into oligomeric compounds via standard peptide linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen bonding. The oligomeric compounds are useful as diagnostic and research reagents.

Abstract: A process for producing a particular nucleic acid sequence from a given sequence of DNA or RNA in amounts which are large compared to the amount initially present, using PNAs in conjunction with the polymerase chain reaction (PCR) is disclosed.

Abstract: Telomerase activity in a sample can be measured using a two reaction protocol involving telomerase substrate and primer extension steps.

Abstract: Disclosed is a substrate useful for separating unmodified and modified mononucleotides and oligonucleotides. The substrate includes at least 12% (weight:volume) polymer in at least 5M urea and at least 32% (volume:volume) organic solvent, the organic solvent being a chemically stable liquid at room temperature and having a dielectric constant of at least 20. Also provided is a method of separating unmodified and modified mononucleotides and/or oligonucleotides utilizing this substrate.

Abstract: 2'-deoxy-2'-alkylnucleotides useful for stabilizing enzymatic nucleic acid molecules and antisense molecules.

Abstract: Specific BRCA1 mutations, PCR primers and hybridization probes are used in nucleic acid-based methods for diagnostic of inheritable breast cancer susceptibility. Additionally, binding agents, such as antibodies, specific for peptides encoded by the subject BRCA1 mutants are used to identify expression products of diagnostic mutations/rare alleles in patient derived fluid or tissue samples. Compositions with high binding affinity for transcription or translation products of the disclosed BRCA1 mutations and alleles are used in therapeutic intervention. Such products include anti-sense nucleic acids, peptides encoded by the subject nucleic acids, and binding agents such as antibodies, specific for such peptides.

Abstract: Nucleic acids can be made available for amplification or other treatment after lysis by contacting the lysate with polyethyleneimine to form a precipitate with the nucleic acids. The nucleic acids are then released from the precipitate by contact with a strong base, and the released nucleic acids are kept in solution with an anionic phosphate ester surfactant. This method for preparing specimen samples is simple and quite rapid.

Abstract: An article suitable for use as a biosensor includes a species of a formula X--R--Ch adhered to a surface of the article as part of a self-assembled monolayer. X is a functionality that adheres to the surface, R is a spacer moiety, and Ch is a chelating agent. A metal ion can be coordinated by the chelating agent, and a polyamino acid-tagged biological binding partner of a target biological molecule coordinated to the metal ion. A method of the invention involves bringing the article into contact with a medium containing or suspected of containing the target biological molecule and allowing the biological molecule to biologically bind to the binding partner. The article is useful particularly as a surface plasmon resonance chip.

Abstract: It has been found that certain glycoproteins, particularly mucins, are inhibitors of nucleic acid amplification reactions and that inhibition of the amplification reaction is associated with partial degradation of the carbohydrate chain. Partial degradation of the carbohydrate of a non-inhibitory glycoprotein renders it inhibitory, and partial degradation of the carbohydrate of a slightly inhibitory glycoprotein makes it more inhibitory. Sample processing prior to amplification may contribute to partial degradation of the carbohydrate chains of the glycoproteins which are present and increase their inhhibitory effect. In contrast, complete removal of the carbohydrate significantly reduces or completely eliminates the inhibitory effect. Methods for reducing or eliminating glycoprotein-associated inhibition of nucleic acid amplification reactions are also disclosed.

Abstract: A scanning probe microscope, such as an atomic force microscope (AFM) or a scanning tunneling microscope (STM), is operated in a stationary mode on a site where an activity of interest occurs to measure and identify characteristic time-varying micromotions caused by biological, chemical, mechanical, electrical, optical, or physical processes. The tip and cantilever assembly of an AFM is used as a micromechanical detector of characteristic micromotions transmitted either directly by a site of interest or indirectly through the surrounding medium. Alternatively, the exponential dependence of the tunneling current on the size of the gap in the STM is used to detect micromechanical movement. The stationary mode of operation can be used to observe dynamic biological processes in real time and in a natural environment, such as polymerase processing of DNA for determining the sequence of a DNA molecule.

Abstract: A method for detecting a target nucleic acid sequence in a sample is provided using hybridization probes which competitively hybridize to a target nucleic acid. According to the method, a target nucleic acid sequence is hybridized to first and second hybridization probes which are complementary to overlapping portions of the target nucleic acid sequence, the first hybridization probe including a first complexing agent capable of forming a binding pair with a second complexing agent and the second hybridization probe including a detectable marker. The first complexing agent attached to the first hybridization probe is contacted with a second complexing agent, the second complexing agent being attached to a solid support such that when the first and second complexing agents are attached, target nucleic acid sequences hybridized to the first hybridization probe become immobilized on to the solid support.

Abstract: Genotypic diagnosis of CADASIL for symptomatic or at risk individuals or fetuses belonging to a family suspected of being affected by CADASIL is carried out by detecting DNA polymorphisms genetically linked to the mutated gene responsible for CADASIL, these DNA polymorphisms being located in the genetic interval of the chromosome 19 flanked by the microsatellites D198221 and D19S215 and including these microsatellites.

Abstract: Modified gene encoding a modified DNA polymerase wherein the modified polymerase incorporates dideoxynucleotides at least 20-fold better compared to the corresponding deoxynucleotides as compared with the corresponding naturally-occurring DNA polymerase.

Abstract: Methods for the use of a class of dyes for improved DNA sequencing are provided. A new class of dyes, BODIPY.RTM. fluorophore, has been described recently. The parent heterocyclic molecule of the BODIPY.RTM. fluorophore is a dipyrrometheneboron difluoride compound which is modified to create a broad class of spectrally-discriminating fluorophores. The present invention provides methods for the use of BODIPY.RTM. fluorophore-labeled DNA. BODIPY.RTM. fluorophore have improved spectral characteristics compared to conventional fluorescein and rhodamine dyes. BODIPY.RTM. fluorophore have narrower band width, insensitivity to solvent or pH, and improved photostability, thus, BODIPY.RTM. fluorophores lead to improved DNA sequencing and/or detection in any method where electrophoresis and detection of DNA is required. Additionally, the spectral properties of the BODIPY.RTM. fluorophores are sufficiently similar in wavelength and intensity to be used with conventional equipment known in the art.

Abstract: Origin of Replication Complex (ORC) genes, nucleic acids which encode ORC proteins and hybridization reagents, probes and primers capable of hybridizing with ORC genes and methods for screening chemical libraries for lead compounds for pharmacological agents useful in the diagnosis or treatment of disease associated undesirable cell growth are provided. An exemplary screen involves forming a mixture comprising a recombinant ORC protein, a natural intracellular ORC protein binding target, and a candidate pharmacological agent; incubating the mixture under conditions whereby, but for the presence of said candidate pharmacological agent, said ORC protein selectively binds said binding target; and detecting the presence or absence of specific binding of said ORC protein to said binding target.

Abstract: The invention relates to nucleic acid molecules which are useful in determining expression of the family of molecules known as the MAGE tumor rejection antigen precursors. These nucleic acid are molecules useful as diagnostic aids for determining whether or not an individual has cancer. Methods using these molecules are also described.

Abstract: An assay for detecting virulent L. monocytogenes is provided. This assay includes the steps of: contacting the nucleic acids of L. monocytogenes with a probe under conditions permitting hybridization; and detecting any probe that hybridizes to the nucleic acids. The probe used in this method includes a DNA sequence selected from a group consisting of a 0.9 kb HindIII-EcoRI fragment of plasmid pLUCH52, or a part thereof; a 1.1 kb HindIII-EcoRI fragment of plasmid pLUCH51, or a part thereof; and a 1.8 kb HindIII-EcoRI fragment of plasmid pLUCH44, or a part thereof).

Abstract: A new human B lymphotropic virus, also designated human herpesvirus-6, has been isolated. DNA, molecular clones, antigenic viral proteins and antibodies having specificity to the new virus have been prepared. Various utilities of the new virus and products derived therefrom have been described.

Abstract: A functionalized, magnetic controlled pore glass support useful in solid phase DNA synthesis is described. The support acts as a universal solid phase for direct oligonucleotide synthesis. The oligonucleotide bound MPG is useful directly to isolate or purify oligonucleotides which possess a section of complementary sequences.