Abstract: The invention concerns thrombin muteins which have the following differences in their sequences as compared with natural thrombin: (a) the exchange of a Gly after Ala, the Gly being in the sequence environment Tyr-Gly-Phe and having position 558 in natural human thrombin (SEQ ID No. 14); (b) at least one exchange or deletion of the following radicals: (b1) His, located in the sequence environment Ala-His-Cys and having position 363 in natural human thrombin (SEQ ID No. 14); (b2) Asp, located in the sequence environment Arg-Asp-Ile and having position 419 in natural human thrombin (SEQ ID No. 14); (b3) Ser, located in the sequence environment Asp-Ser-Gly and having position 525 in natural human thrombin (SEQ ID No. 14). The invention further concerns the use of these muteins as antidotes.

Abstract: A method for the detection of a polynucleotide target sequence is described. The method involves the formation of a covalent or non-covalent bonded pair of nucleotide sequences formed in response to a target polynucleotide sequence, adding nucleotide sequence specific binding proteins each capable of binding one member of the pair of nucleotide sequences, and detecting the specific binding proteins complexed to the pair of nucleotide sequences.

Abstract: Method and compositions are provided for analyzing nucleic acid sequences based on repeated cycles of duplex extension along a single stranded template. Preferably, such extension starts from a duplex formed between an initializing oligonucleotide and the template. The initializing oligonucleotide is extended in an initial extension cycle by ligating an oligonucleotide probe to its end to form an extended duplex. The extended duplex is then repeatedly extended by subsequent cycles of ligation. During each cycle, the identity of one or more nucleotides in the template is determined by a label on, or associated with, a successfully ligated oligonucleotide probe. Preferably, the oligonucleotide probe has a blocking moiety, e.g. a chain-terminating nucleotide, in a terminal position so that only a single extension of the extended duplex takes place in a single cycle. The duplex is further extended in subsequent cycles by removing the blocking moiety and regenerating an extendable terminus.

Abstract: There is disclosed herein an invention which relates to the fields of genetic engineering, microbiology, and computer science, that allows a user, whether they be a molecular biologist or a clinical diagnostician, to calculate and design extremely specific oligonucleotide probes for DNA and mRNA hybridization procedures. The probes designed with this invention may be used for medical diagnostic kits, DNA identification, and potentially continuous monitoring of metabolic processes in human beings. The key features design oligonucleotide probes based on the GenBank database of DNA and mRNA sequences and examine candidate probes for specificity or commonality with respect to a user-selected experimental preparation. Two models are available: a Mismatch Model, that employs hashing and continuous seed filtration, and an H-Site Model, that analyzes candidate probes for their binding specificity relative to some known set of mRNA or DNA sequences.

Abstract: Disclosed are methods of producing a synthetic oligonucleotide of selected nucleotide sequence which is internally functionalized at least one selected location with an aminoalkylphosphotriester, and labelled with a nonradioactive material. Also disclosed are oligonucleotides produced by this method.