合成核苷和核苷酸。43. 碳环氧杂环丁烷菌素G（C.OXT-G）三磷酸类似物对脊椎动物端粒酶的抑制作用以及C.OXT-G处理对人HL60细胞端粒长度的影响。

Synthetic nucleosides and nucleotides. 43. Inhibition of vertebrate telomerases by carbocyclic oxetanocin g (C.OXT-G) triphosphate analogues and influence of C.OXT-G treatment on telomere length in human HL60 cells.

作者信息

Yamaguchi Toyofumi, Saneyoshi Mineo, Takahashi Hazuki, Hirokawa Sachiko, Amano Rie, Liu Xiaohong, Inomata Motoko, Maruyama Tokumi

机构信息

Department of Biosciences and Biotechnology Research Center, Teikyo University of Science and Technology, Uenohara, Yamanashi, Japan.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2006;25(4-6):539-51. doi: 10.1080/15257770600684217.

DOI:10.1080/15257770600684217

PMID:16838844

Abstract

Telomerase, responsible for telomere synthesis, is expressed in approximately 90% of human tumor cells but seldom in normal somatic cells. In this study, inhibition by carbocyclic oxetanocin G triphosphate (C. OXT-GTP) and its analogues was investigated in order to clarify the susceptibility of telomerase to various nucleotide analogues. C. OXT-GTP competitively inhibited telomerase activity with respect to dGTP However, C. OXT-GTP had a potent inhibitory effect on DNA polymerase alpha. It was examined whether the nucleoside (C. OXT-G) was able to alter telomere length in cultured human HL60 cells. Contrary to expectation, long-term treatment with 10 microM C. OXT-G was found to cause telomere lengthening.

摘要

端粒酶负责端粒的合成，约90%的人类肿瘤细胞中可检测到它的表达，而在正常体细胞中则很少表达。在本研究中，为了阐明端粒酶对各种核苷酸类似物的敏感性，研究了碳环氧杂环丁烷三磷酸鸟苷（C. OXT-GTP）及其类似物对端粒酶的抑制作用。C. OXT-GTP相对于dGTP竞争性抑制端粒酶活性。然而，C. OXT-GTP对DNA聚合酶α有很强的抑制作用。研究了核苷（C. OXT-G）是否能够改变培养的人HL60细胞中的端粒长度。与预期相反，发现用10微摩尔C. OXT-G进行长期处理会导致端粒延长。