Abstract: This invention is directed to methods, kits and compositions pertaining to PNA Molecular Beacons. PNA Molecular Beacons comprise self-complementary arm segments and flexible linkages which promote intramolecular or intermolecular interactions. In the absence of a target sequence, PNA Molecular Beacons facilitate efficient energy transfer between the linked donor and acceptor moieties of the probe. Upon hybridization of the probe to a target sequence, there is a measurable change in at least one property of at least one donor or acceptor moiety of the probe which can be used to detect, identify or quantitate the target sequence in a sample.

Abstract: This invention pertains to solubility enhanced polymers and methods, kits and compositions which enhance the aqueous solubility of said polymers. One set of preferred methods, kits and compositions embody or utilize phosphorous containing synthons and are most useful for modulating the solubility of synthetic nucleic acids and synthetic nucleic acid analogs. A second set of preferred methods, kits and compositions are most useful for modulating the aqueous solubility of peptides, other polyamides and most preferably peptide nucleic add (PNA) polymers.

Abstract: The present invention relates to methods, kits and compositions suitable for the improved detection, quantitation and analysis of nucleic acid target sequences using probe-based hybridization assays.

Abstract: A method is disclosed for the preparation of novel PNA synthons compatible with DNA synthetic reagents and instrumentation. Accordingly, the PNA synthons of this invention are particularly suitable for the preparation of PNA-DNA chimeras, among other oligomers. The PNA synthons are designed to have a protecting group strategy which is orthogonal and allows removal of the protecting groups under mild conditions. Generally, an acid labile protected backbone is coupled to a nucleobase side chain moiety to form the PNA synthon. A novel method for synthesizing the acid labile protected backbone also is described. In addition, novel compositions of matter are disclosed.

Abstract: A method is disclosed for preparing novel PNA synthons having protecting groups capable of removal under mild conditions. The PNA synthons are prepared by coupling novel N-substituted nucleobase intermediates having carbamate protection of the exocyclic amino group of the heterocycle to an amino protected backbone or an amino protected backbone ester of the amino acid N-(2-aminoethyl)-glycine. By the method of this invention, the resultant PNA synthons can have orthogonal protection of the carbamate protected nucleobase and the amino protected backbone. The PNA synthons are useful in the synthesis of peptide nucleic acids (PNAs) and other oligomers such as PNA-DNA chimeras, and may be used in automated synthesizers. Novel compositions of matter are also disclosed. In addition, a guanine PNA synthon having selective carbamate protection of the exocyclic 2-amino group with the C6 carbonyl group unprotected is disclosed.

Abstract: A method is disclosed for preparing novel purine PNA synthons having protecting groups which may be removed under mild conditions. The purine PNA synthons generally are prepared by coupling purine derivatives having carbamate protection to a protected N-(2-aminoethyl)-glycine backbone. By a method of this invention, purine PNA synthons may have orthogonal protection of the carbamate protected purine and the protected backbone. The purine PNA synthons are useful in the synthesis of peptide nucleic acids (PNAs) and other oligomers such as PNA-DNA chimeras, and may be used in automated synthesizers. In practicing methods of the invention, novel compositions of matter also are disclosed.

Abstract: This invention relates to methods, kits and compositions suitable for the improved detection, analysis and quantitation of nucleic acid target sequences using probe based hybridization assays. The invention is more specifically directed to methods, kits and compositions suitable for suppressing the binding of detectable nucleic acid probes or detectable PNA probes to non-target nucleic acid sequences in an assay for a target nucleic acid sequence to thereby improve the reliability, sensitivity and specificity of the assay. The methods, kits and compositions of this invention are particularly well suited to the detection and analysis of nucleic acid point mutations.

Abstract: A method is disclosed for the preparation of novel PNA synthons compatible with DNA synthetic reagents and instrumentation. Accordingly, the PNA synthons of this invention are particularly suitable for the preparation of PNA-DNA chimeras, among other oligomers. The PNA synthons are designed to have a protecting group strategy which is orthogonal and allows removal of the protecting groups under mild conditions. Generally, an acid labile protected backbone is coupled to a nucleobase side chain moiety to form the PNA synthon. A novel method for synthesizing the acid labile protected backbone also is described. In addition, novel compositions of matter are disclosed.

Abstract: A method and apparatus for sequentially degrading at least a portion of a polymer of backbone repeating units, the polymer having a terminal repeating unit comprised of a nucleophile and a backbone carbonyl carbon distant from the nucleophile, comprising the steps of first initiating attack of said nucleophile upon said backbone carbonyl carbon by raising the energy level to activate said nucleophile for said attack. Secondly, forming a ring comprising the terminal repeating unit, thereby simultaneously releasing the ring and generating a shortened polymer having a terminal repeating unit capable of nucleophile attack upon the backbone carbonyl carbon and, lastly, maintaining the reaction conditions necessary for repeating steps a and b until the portion of the polymer desired is degraded.

Abstract: The invention pertains to compounds and methods for the reversible modification of natural products, biopolymers or synthons for natural products or biopolymers, such as nucleosides, nucleotides, and oligonucleosides. The modification enables one to perform a variety of chemistries on these compounds, yet can be removed to regenerate functional groups on the natural products, biopolymer or synthon of interest.

Abstract: A method for analysis of peptides and proteins. A peptide or protein is exposed to a coupling reagent and a buffer. The coupling reagent derivatizes the terminal amino acid residue of the peptide or protein. A cleaving-reagent is then passed across the peptide or protein in the form of a spray to cleave the derivatized terminal amino acid residue from the peptide or protein. The apparatus includes a suitable support on which a peptide or protein can be disposed. The support is disposed in a reaction chamber. Pressurized sources of a suitable coupling reagent and a buffer are connected to the reaction chamber to allow exposure of the peptide or protein on the support to the coupling reagent and the buffer. A valve is also connected to the reaction chamber. The valve includes a sliding member which causes a gas and a liquid cleaving reagent to combine, whereby a spray is formed which is conducted from the valve to the reaction chamber.

Abstract: The invention pertains to a method for immobilizing proteins or peptides onto a flat, microporous membrane surface in a form suitable for sequence analysis or other chemical or enzymatic processes. The process involves the formation of a thin polymer network that entraps the protein or peptide therein.

Abstract: A membrane suitable for immobilizing peptides and proteins is disclosed. The membrane is a flexible, polymeric, porous membrane which contains functional groups capable of covalently linking the peptides and proteins. The functional groups can be provided by reacting the membrane itself or a coating thereon with nucleophiles which provide --NH.sub.2, --SH, --OH or --COOH functionality to the membrane surface. Additionally, surfaces containing --NH.sub.2 groups can be further reacted with diisothiocyantes to provide an isothiocyanate functionality having enhanced covalent binding characteristics.

Abstract: A method is provided for synthesizing oligonucleotides and peptides directly onto a membrane. The method provides a means for generating membrane affinity supports. A modified membrane for the method of direct synthesis is also provided.