Tissue plasminogen activator variants
    22.
    发明授权
    Tissue plasminogen activator variants 失效
    组织纤溶酶原激活物变体

    公开(公告)号:US5714372A

    公开(公告)日:1998-02-03

    申请号:US306928

    申请日:1994-09-15

    摘要: Biologically active mutant tissue plasminogen activators are disclosed wherein site directed mutagenesis, for example, of a two-chain activation site renders said mutants resistant to conversion to the two-chain form. In addition, mutant tissue plasminogen activators are disclosed which have amino acid substitutions or deletions in the region of positions 274-277, which may or may not be resistant to conversion to the two-chain form, but show enhanced fibrin specificity relative to wild-type tissue plasminogen activator.

    摘要翻译: 公开了生物活性突变组织纤溶酶原激活剂,其中例如双链激活位点的定点诱变使所述突变体对转化为双链形式具有抗性。 此外,公开了突变组织纤溶酶原激活剂,其在位置274-277的区域具有氨基酸取代或缺失,其可能或可能不耐转化为双链形式,但相对于野生型的纤维蛋白特异性显示出增强的纤维蛋白特异性, 型组织纤溶酶原激活物。

    Methods and compositions for determining the sequence of nucleic acids
    24.
    发明授权
    Methods and compositions for determining the sequence of nucleic acids 失效
    用于确定核酸序列的方法和组合物

    公开(公告)号:US5403708A

    公开(公告)日:1995-04-04

    申请号:US909165

    申请日:1992-07-06

    摘要: Methods and compositions for forming ligation product hybridized to a nucleic acid template. The ligation product is formed by contacting a nucleic acid template with a primer capable of hybridizing to the template to form a primed template. The primed template is then contacted with a pool of random extension oligonucleotides of length N and an enzyme system. The enzyme system is capable of covalently linking the primer to an extension oligonucleotide adjacently hybridized to it and one or more other extension oligonucleotides adjacently hybridized to the ligation product defined by covalently linked ligation primer and one or more extension oligonucleotides. When covalently linked, the ligation product is hybridized to the nucleic acid template. Modifications permit the determination of the nucleotide sequence of one or more members of a first set of target nucleotide residues in the nucleic acid template that are spaced at intervals of N nucleotides. In such sequencing methods, labeled ligation product is formed wherein the position and type of label incorporated into the labeled ligation product provides information concerning the nucleotide residue in the nucleic acid template with which the labeled nucleotide residue is base paired. The compositions comprise a pool of oligonucleotides of a predetermined length N containing at least one differentially labeled sequencing nucleotide residue at a predetermined position and random nucleotide residues at each of the other nucleotide positions.

    摘要翻译: 用于形成与核酸模板杂交的连接产物的方法和组合物。 通过使核酸模板与能够与模板杂交的引物接触以形成引发的模板来形成连接产物。 然后将引发的模板与长度为N和酶系统的随机延伸寡核苷酸库接触。 酶系统能够共价连接引物与与其相邻杂交的延伸寡核苷酸和与由共价连接的连接引物和一个或多个延伸寡核苷酸定义的连接产物相邻杂交的一个或多个其它延伸寡核苷酸。 当共价连接时,连接产物与核酸模板杂交。 修饰允许确定间隔N个核苷酸的核酸模板中第一组靶核苷酸残基的一个或多个成员的核苷酸序列。 在这样的测序方法中,形成标记的连接产物,其中结合到标记的连接产物中的标记的位置和类型提供了与标记的核苷酸残基是碱基配对的核酸模板中的核苷酸残基有关的信息。 组合物包含预定长度N的寡核苷酸库,其在预定位置含有至少一个差异标记的测序核苷酸残基,并且在每个其它核苷酸位置处含有随机核苷酸残基。