scholarly journals Telomerase Inhibition Studies of Novel Spiroketal-Containing Rubromycin Derivatives

2013 ◽  
Vol 66 (5) ◽  
pp. 530 ◽  
Author(s):  
Tsz-Ying Yuen ◽  
Yu-Pong Ng ◽  
Fanny C. F. Ip ◽  
Jack L.-Y. Chen ◽  
Darcy J. Atkinson ◽  
...  

Twenty nine novel spiroketal derivatives related to the rubromycins were evaluated for their anti-telomerase activity using the real-time quantitative telomeric repeat amplification protocol assay. The parent compound γ-rubromycin exhibited the highest potency against human telomerase activity within the series. Modification of the spiroketal motif by the introduction of heteroatoms and substituents at different positions produced analogues with varying bioactivity. Variation at the isocoumarin subunit of the title compound resulted in weaker activity, indicative of its importance in telomerase inhibition.

2001 ◽  
Vol 47 (3) ◽  
pp. 519-524 ◽  
Author(s):  
Mi Hou ◽  
Dawei Xu ◽  
Magnus Björkholm ◽  
Astrid Gruber

Abstract Background: Telomerase is a ribonucleoprotein enzyme associated with immortalization and transformation of human cells. The telomeric repeat amplification protocol (TRAP) is widely used for the detection of telomerase activity. The TRAP method, although highly sensitive and specific because it includes PCR amplification, is laborious and does not provide precise quantitative information. Methods: We developed a real-time quantitative TRAP (RTQ-TRAP) system by combining a real-time PCR technique with the conventional TRAP method. Telomerase activity in human tumor cell lines and in 13 lymphoma samples was measured using the RTQ-TRAP assay, and the results obtained from the samples using the RTQ-TRAP method were compared with the conventional TRAP method. Results: The RTQ-TRAP method was both accurate and reproducible in measuring telomerase activity in a dilution series of protein extracts from HL60 cells. Telomerase activity in 13 lymphoma samples, as determined by the RTQ-TRAP method, was ninefold lower than that measured by the conventional TRAP method. The half-life of telomerase activity in human tumor cells, as determined using RTQ-TRAP, was much shorter than the half-life reported previously. Conclusions: Our results suggest that the conventional TRAP assay frequently overestimates telomerase activity in tumor samples. The RTQ-TRAP method is thus a useful tool to rapidly and precisely quantify telomerase activity.


Author(s):  
Aleksandra R. Vukašinović ◽  
Jelena M. Kotur-Stevuljević ◽  
Vid Mlakar ◽  
Miron D. Sopić ◽  
Zorica P. Cvetković ◽  
...  

2006 ◽  
Vol 1 (3) ◽  
pp. 1583-1590 ◽  
Author(s):  
Brittney-Shea Herbert ◽  
Amelia E Hochreiter ◽  
Woodring E Wright ◽  
Jerry W Shay

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