Methods for measuring telomere length
    9.
    发明授权
    Methods for measuring telomere length 失效
    测定端粒长度的方法

    公开(公告)号:US5834193A

    公开(公告)日:1998-11-10

    申请号:US660402

    申请日:1996-06-07

    CPC分类号: C12Q1/6816

    摘要: Methods and compositions for the measurement of telomere length have application in medical diagnostic, prognostic, and therapeutic procedures. The methods for measuring telomere length include primer extension-based methods and probe-based methods. The primer extension methods involve elongation of telomeric, linker, and/or subtelomeric based primers under conditions such that the telomere serves as a template for primer extension and that the resultant primer extension products can be compared to standards of known length to provide a measure of telomere length. The probe based methods allow for telomere length measurements using DNA from lysed or whole cells and involve hybridizing an excess of probe to all telomeric repeat sequences in the telomere, measuring the amount of bound probe, and correlating the amount of bound probe measured with telomere length.

    摘要翻译: 用于测量端粒长度的方法和组合物可用于医学诊断,预后和治疗程序。 测量端粒长度的方法包括基于引物延伸的方法和基于探针的方法。 引物延伸方法涉及在使得端粒作为引物延伸的模板的条件下延伸端粒末端,接头和/或亚端粒基引物,并且所得到的引物延伸产物可以与已知长度的标准物进行比较, 端粒长度 基于探针的方法允许使用来自裂解的全细胞的DNA进行端粒长度测量,并且包括将过量的探针与端粒中的所有端粒重复序列杂交,测量结合的探针的量,并将测量的结合的探针的量与端粒长度相关联 。

    Telomerase inhibitors
    10.
    发明授权

    公开(公告)号:US5760062A

    公开(公告)日:1998-06-02

    申请号:US425043

    申请日:1995-04-18

    CPC分类号: C07D495/04

    摘要: Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds that are derivatives of pyrido�b!thiophenes, pyrido�b!furans, pyridine ethers or pyridine thioethers. Such compounds are characterized by the following structure: ##STR1## X.sub.3 is oxygen or sulfur; and the double dashed lines between X.sub.4 and X.sub.5 indicate an optional double bond, which, when present, forms a fused, bicyclic pyrido�b!furan or pyrido�b!thiophene ring system, depending upon whether X.sub.3 is oxygen or sulfur, respectively. When the double bond is not present, the compound is a monocyclic pyridine ether or thioether, again depending upon whether X.sub.3 is oxygen or sulfur. X.sub.4 is --CH.sub.2 R.sub.21 or --CR.sub.21 --, where R.sub.21 is selected from the group consisting of aryl, heteroaryl, aralkyl, heteroaralkyl, alkylcarbonyl, arylcarbonyl, heteroalkylcarbonyl, heteroaralkylcarbonyl, aralkylcarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylarninocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl and arylsulfonyl; and X.sub.5 is hydrogen, alkyl, hydroxyl, alkoxyl, aryloxyl, halogen, cyano, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl, arylsulfonyl or --CR.sub.22 -- where R.sub.22 is selected from the group consisting of hydrogen, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, hydroxyl, halogen, cyano, carboxyl, alkoxycarbonyl and aryloxycarbonyl. When X.sub.4 is --CR.sub.21 --, X.sub.5 is --CR.sub.22 --, and X.sub.4 and X.sub.5 are joined by the above-mentioned double bond, to form thereby a fused, bicyclic pyrido�b!thiophene (X.sub.3 is sulfur) or pyrido�b!furan (X.sub.3 is oxygen) ring system. When X.sub.4 is --CH.sub.2 R.sub.21, X.sub.5 is not --CR.sub.22 --, thereby forming a pyridine ether (X.sub.3 is oxygen) or thioether (X.sub.3 is sulfur). R.sub.18 and R.sub.19 are selected independently from the group consisting of hydrogen, halogen, hydroxy, aryloxy, alkoxy, lower alkyl, aryl, heteroaryl, aralkyl and heteroaralkyl. R.sub.20 is selected from the group consisting of alkoxymethyl, dialkoxymethyl, arylalkylaminomethyl, arylaminomethyl, alkylaminomethyl, aminomethyl, diarylaminomethyl, dialkylaminomethyl, hydroximinyl, iminyl, aldehyde, alkylcarbonyl, arylcarbonyl, alkyliminyl, aryliminyl, aralkyliminyl, alkoximinyl, aryloximinyl, heterocycleimninyl, alkoxycarbonyl, aryloxycarbonyl, carboxyl, alkene, --HC.dbd.NNHR.sub.23 where R.sub.23 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heterocycle, heterocyclealkyl, and --C(X.sub.6)NHR.sub.24 where X.sub.6 is oxygen or sulfur and R.sub.24 is selected from the group consisting of hydrogen, aryl, arylsulfonyl, aralkyl, heterocycle and heterocyclealkyl.