摘要:
A method is described for generating blended nucleic acid ligands containing non-nucleic acid functional units. Specifically, a SELEX identified RNA ligand to the integrin gpIIbIIIa is conjugated to the peptide Gly-Arg-Gly-Asp-Thr-Pro (SEQ ID NO:1). This blended RNA ligand inhibits the biological activity of gpIIbIIIa with high specificity. Also described is a single-stranded DNA ligand to elastase coupled to N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl (SEQ ID NO:2) ketone. This elastase blended nucleic acid ligand inhibits the biological activity of elastase.
摘要翻译:描述了一种用于产生含有非核酸功能单元的混合核酸配体的方法。 具体地,将SELEX鉴定的整合素gpIIbIIIa的RNA配体与肽Gly-Arg-Gly-Asp-Thr-Pro(SEQ ID NO:1)缀合。 这种混合RNA配体以高特异性抑制gpIIbIIIa的生物活性。 还描述了与N-甲氧基琥珀酰基-Ala-Ala-Pro-Val-氯甲基(SEQ ID NO:2)酮偶联的弹性蛋白酶的单链DNA配体。 该弹性蛋白酶共混核酸配体抑制弹性蛋白酶的生物活性。
摘要:
Nucleic acid ligands containing modified nucleotides are described as are methods for producing such oligonucleotides. Such ligands enrich the chemical diversity of the candidate mixture for the SELEX process. Specific examples are provided of nucleic acids containing nucleotides modified at the 2'- and 5-position. Specific 2-OH and 2'-NH.sub.2 modified RNA ligands to thrombin are described.
摘要:
Compounds of the formula ##STR1## wherein: R.sub.1, R.sub.2, R.sub.3 and R.sub.4, which may be the same or different, are selected from the group consisting of hydrogen, alkyl of 1-6 carbons, cycloalkyl of 3 to 6 carbons, alkenyl of 2-6 carbons, or together represent methylene groups --(CH.sub.2).sub.n --where n is a whole number from 1 to 6, provided that R.sub.1 and R.sub.2 or R.sub.3 and R.sub.4 are not both hydrogen;R.sub.5 and R.sub.6, which may be the same or different, are selected from the group consisting of hydrogen, halogen, nitro or --S(O).sub.n R.sub.7 where n is 0, 1 or 2 and R.sub.7 is an optionally substituted alkyl of 1-12 carbons atoms; and both Ar substituents are optionally substituted heteroaromatic rings or one Ar is such heteroaromatic ring and the other is optionally substituted phenyl, the optional substitution for Ar being halogen, nitro or --S(O).sub.n R.sub.7 where n and R.sub.7 have the value given above. The compounds are useful as inhibitors of human neutrophil elastase.
摘要翻译:式(I)的化合物其中:R 1,R 2,R 3和R 4可以相同或不同,选自氢, 1-6个碳原子的烷基,3至6个碳原子的环烷基,2-6个碳烯基,或一起表示亚甲基 - (CH 2)n - ,其中n为1至6的整数,条件是R1和R2或R3 和R4不同时为氢; R 5和R 6可以相同或不同,选自氢,卤素,硝基或-S(O)n R 7,其中n为0,1或2,R 7为1-12的任选取代的烷基 碳原子; 并且两个Ar取代基是任选取代的杂芳环,或者一个Ar是这样的杂芳环,另一个是任选取代的苯基,任选地取代Ar是卤素,硝基或-S(O)n R 7,其中n和R 7具有上面给出的值。 该化合物可用作人中性粒细胞弹性蛋白酶的抑制剂。
摘要:
A method is described for generating blended nucleic acid ligands containing non-nucleic acid functional units. Specifically, a SELEX identified RNA ligand to the integrin gpIIbIIIa is conjugated to the peptide Gly-Arg-Gly-Asp-Thr-Pro (SEQ ID NO:1). This blended RNA ligand inhibits the biological activity of gpIIbIIIa with high specificity. Also described is a single-stranded DNA ligand to elastase coupled to N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl ketone (SEQ ID NO:2). This elastase blended nucleic acid ligand inhibits the biological activity of elastase.
摘要翻译:描述了一种用于产生含有非核酸功能单元的混合核酸配体的方法。 具体地,将SELEX鉴定的整合素gpIIbIIIa的RNA配体与肽Gly-Arg-Gly-Asp-Thr-Pro(SEQ ID NO:1)缀合。 这种混合RNA配体以高特异性抑制gpIIbIIIa的生物活性。 还描述了与N-甲氧基琥珀酰基-Ala-Ala-Pro-Val-氯甲基酮(SEQ ID NO:2)偶联的弹性蛋白酶的单链DNA配体。 该弹性蛋白酶共混核酸配体抑制弹性蛋白酶的生物活性。
摘要:
Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule. The nucleosides can be used to prepare oligonucleotides for use in various applications, either alone or in combination with other modified nucleosides and/or naturally occurring nucleosides.
摘要:
Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule. The nucleosides can be used to prepare oligonucleotides for use in various applications, either alone or in combination with other modified nucleosides and/or naturally occurring nucleosides.
摘要:
Nucleic acid ligands containing modified nucleotides are described as are methods for producing such oligonucleotides. Such ligands enrich the chemical diversity of the candidate mixture for the SELEX process. Specific examples are provided of nucleic acids containing nucleotides modified at the 2′- and 5-position. Specific 2-OH and 2′-NH2 modified RNA ligands to thrombin are described.