1999 Fiscal Year Final Research Report Summary
Molecular designing of nucleoside analogues for inhibitor of telomerase
| Project/Area Number |
10672097
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Teikyo University of Science & Technology |
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Principal Investigator |
SANEYOSHI Mineo Teikyo University of Science & Technology, Undergraduate School of Science & Engineering, Professor, 理工学部, 教授 (20002339)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Toyofumi Teikyo University of Science & Technology, Undergraduate School of Science & Engineering, Assistant Professor, 理工学部, 講師 (90230367)
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| Project Period (FY) |
1998 – 1999
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| Keywords | telomerase / stretch PCR / L-dGTP / L-dTTP / 5-styryl araUTP / HEPT / araUTP / lyxosyl nucleotides |
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| Research Abstract |
Molecular designing of nucleosides and corresponding 5'-triphosphates as potential selective inhibitor for human telomerase have been considered.
First, we have examined the stretch PCR method for determination of HeLa cell telomerase in detail. The results obtained could be used in following experiments including enzyme kinetic analysis by Lineweaver-Burk plots. L-dGTP and L-dTIP, enantiomers of natural substrates dGTP and dTTP, showed inhibitory effect on telomerase in lesser extent when compared with HIV-1 reverse transcriptase. This result clearly indicated that telomerase can strictly recognize enantiomer for its substrate, On the other hand, a 5-styryl-substituted dUTP analogue has shown strong affinity to the telomerase, thus this enzyme was prefer hydrophobic and steric substituent no base moieties. Based on these findings, several dTTP analogues such as 5-azidomethyl-, aminomethyl-, hydroxymethyl- and methoxymethly-derivatives were synthesized, additionally, sugar replacement lyxofuranosyl nucleotides having various aglycon moieties were also prepared. As the other source for telomerase, cherry salmon tests were investigated and found strong telomerase activity. These findings should be applicable to further studies of the enzyme on the level of protein structure and function.
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