Abstract: The invention provides a collection of probes useful for hybridizing to a target nucleic acid. The probes associate with each other, binding with high affinity to the target nucleic acid, to form three-way junctions and other complexes. At least one of the probes in each collection includes a nucleic acid analog. Methods using the probes in hybridization and as primers are also provided.

Abstract: The invention provides methods, kits, and compositions for ligation of PNA-DNA chimeric probes and oligonucleotides when they are hybridized adjacently to template nucleic acids using ligases and ligation reagents. Structural requirements of the chimeras for ligation include 5 to 15 contiguous PNA monomer units, 2 or more contiguous nucleotides, and a 3′ hydroxyl or 5′ hydroxyl terminus. The chimera and/or oligonucleotide may be labelled with fluorescent dyes or other labels. The methods include, for example, oligonucleotide-ligation assays (OLA) and single nucleotide polymorphism detection.

Abstract: A chemical moiety including a polymer (P), a first tethering element (T), a ligand (L) which is a specific sequence of PNA, a second tethering element (T′) and a quencher (Q) is disclosed. In the absence of a complement to the PNA sequence, the PNA is in a tightly coiled configuration, thereby quenching the polymer due to the close proximity of the quencher to the polymer. When a receptor is added that recognizes the PNA sequence, a hybridization of the PNA sequence separates the polymer and the quencher, resulting in an increase of detected fluorescence. The same chemistry is advantageously employed in a competitive assay. A method for detecting nucleic acids in a target sample using the PTLT′Q molecule is also disclosed.

Abstract: The present invention pertains to certain nucleic acid analogs and related kits that are useful for the capture, recognition, detection, identification, or quantification of certain chemical or biological entities.

Abstract: The invention provides methods, kits, and compositions for ligation of PNA-DNA chimeric probes and oligonucleotides when they are hybridized adjacently to template nucleic acids using ligases and ligation reagents. Structural requirements of the chimeras for ligation include 5 to 15 contiguous PNA monomer units, 2 or more contiguous nucleotides, and a 3′ hydroxyl or 5′ hydroxyl terminus. The chimera and/or oligonucleotide may be labelled with fluorescent dyes or other labels. The methods include, for example, oligonucleotide-ligation assays (OLA) and single nucleotide polymorphism detection.

Abstract: A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. The peptide nucleic acids of the invention comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone. Some PNAs of the invention also contain C1-C8 alkylamine side chains.

Abstract: The invention provides a collection of probes useful for hybridizing to a target nucleic acid. The probes associate with each other, binding with high affinity to the target nucleic acid, to form three-way junctions and other complexes. At least one of the probes in each collection includes a nucleic acid analog. Methods using the probes in hybridization and as primers are also provided.

Abstract: Novel peptide nucleic acids and novel linked peptide nucleic acids, form triple stranded structures with nucleic acids. The peptide nucleic acids include ligands such as naturally occurring nucleobases attached to a peptide backbone through a suitable linker. Other nucleobases including C-pyrimidines and iso-pyrimidines can be used as the ligands in Hoogsteen strands to increase binding affinity. Two peptide nucleic acid strands are joined together with a linker to form a bis-peptide nucleic acid. The individual strands of the peptide nucleic acids in the bis compounds can be orientated either parallel or antiparallel to each other.

Abstract: Novel peptide nucleic acids and novel linked peptide nucleic acids, form triple stranded structures with nucleic acids. The peptide nucleic acids include ligands such as naturally occurring nucleobases attached to the peptide backbone through a suitable linker. Other nucleobases including C-pyrimidines and iso-pyrimidines can be used as the ligands in Hoogsteen strands to increase binding affinity. Two peptide nucleic acid strands are joined together with a linker to form a bis-peptide nucleic acid. The individual strands of the peptide nucleic acids in the bis compounds can be oriented either parallel or antiparallel to each other.

Abstract: Binary probe and clamp compositions conduct methods for target hybridization detection. Where the probe is a substrate for exonuclease cleavage, the composition provides quantitation and detection of PCR products, by real-time and end-point measurements. Where the probe is an amplification primer, the composition provides an improved method for labelling and detection of PCR products. Probes and clamps may be labelled with fluorescent dyes, quenchers, hybridization-stabilizing moieties, chemiluminescent dyes, and affinity ligands. Clamps may be nucleic acid analogs, such as 2-aminoethylglycine PNA.

Abstract: A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. The peptide nucleic acids of the invention comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone. Some PNAs of the invention also contain C1-C8 alkylamine side chains.

Abstract: A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.

Abstract: Methods of capture, recognition, detection, identification or quantitation of nucleic acids and diagnostics uses generally are described in which are used: (a) a peptide nucleic acid (PNA) comprising a polyamide backbone bearing a plurality of ligands at respective spaced locations along said backbone, said ligands being each independently naturally occurring nucleobases, non-naturally occurring nucleobases or nucleobase-binding groups, each said ligand being bound directly or indirectly to a nitrogen atom in said backbone, and said ligand bearing nitrogen atoms mainly being separated from one another in said backbone by from 4 to 8 intervening atoms; or (b) a nucleic acid analogue capable of hybridizing to a nucleic acid of complementary sequence to form a hybrid which is more stable against denaturation by heat than a hybrid between the conventional deoxyribonucleotide corresponding to said analogue and said nucleic acid; or (c) a nucleic acid analogue capable of hybridizing to a double stranded nucleic aci

Abstract: A method composition and apparatus for the hybridization and separation of molecules having a desired target sequence in a sample by contacting a sample of single stranded nucleic acids with a detectable PNA probe having a sequence complementary to the target sequence so that the target sequence, if present, will hybridize with the detectable probe to form a detectable duplex, and then separating the duplex in a denaturing medium from unbound sample components by electrophoresis. The invention also relates to methods compositions and apparatus for the hybridization and separation of molecules having a desired target sequence in a mixed sample of single stranded nucleic acids and their complementary strands by contacting the sample with a detectable PNA probe.

Abstract: The invention provides compositions and methods suitable for dissolving nucleic acid analogs with uncharged, neutral backbones at high concentrations at approximately neutral pH. By using the compositions of the invention, which include a polar, aprotic solvent, concentrations of nucleic acid analogs such as PNA can be achieved in the range of approximately 1 &mgr;M to 10 mM.

Abstract: The invention provides methods and a kit for primer extension of PNA-DNA chimera from template nucleic acids using polymerases, nucleotide 5′-triphosphates, and primer extension reagents. Structural requirements of the chimera for primer extension include 5 to 15 contiguous PNA monomer units, 3 or more contiguous nucleotides, and a 3′ hydroxyl terminus. The chimera and/or a nucleotide is labelled with fluorescent dyes or other labels. The methods include DNA sequencing, DNA fragment analysis, reverse transcription, mini-sequencing, chromosome labelling, amplification, and single nucleotide polymorphism (SNP) detection.

Abstract: The invention provides methods, kits, and compositions for ligation of PNA-DNA chimeric probes and oligonucleotides when they are hybridized adjacently to template nucleic acids using ligases and ligation reagents. Structural requirements of the chimeras for ligation include 5 to 15 contiguous PNA monomer units, 2 or more contiguous nucleotides, and a 3′ hydroxyl or 5′ hydroxyl terminus. The chimera and/or oligonucleotide may be labelled with fluorescent dyes or other labels. The methods include, for example, oligonucleotide-ligation assays (OLA) and single nucleotide polymorphism detection.

Abstract: A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.

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.