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10.1002/cbic.200800491

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C7161993!7161993 !19031435
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suck abstract from ncbi


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pmid19031435
      Chembiochem 2008 ; 9 (18 ): 3037-45
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  • Differential inhibitory activities and stabilisation of DNA aptamers against the SARS coronavirus helicase #MMPMID19031435
  • Shum KT ; Tanner JA
  • Chembiochem 2008[Dec]; 9 (18 ): 3037-45 PMID19031435 show ga
  • The helicase from severe acute respiratory syndrome coronavirus (SARS-CoV) possesses NTPase, duplex RNA/DNA-unwinding and RNA-capping activities that are essential for viral replication and proliferation. Here, we have isolated DNA aptamers against the SARS-CoV helicase from a combinatorial DNA library. These aptamers show two distinct classes of secondary structure, G-quadruplex and non-G-quadruplex, as shown by circular dichroism and gel electrophoresis. All of the aptamers that were selected stimulated ATPase activity of the SARS-CoV helicase with low-nanomolar apparent K(m) values. Intriguingly, only the non-G-quadruplex aptamers showed specific inhibition of helicase activities, whereas the G-quadruplex aptamers did not inhibit helicase activities. The non-G-quadruplex aptamer with the strongest inhibitory potency was modified at the 3'-end with biotin or inverted thymidine, and the modification increased its stability in serum, particularly for the inverted thymidine modification. Structural diversity in selection coupled to post-selection stabilisation has provided new insights into the aptamers that were selected for a helicase target. These aptamers are being further developed to inhibit SARS-CoV replication.
  • |Aptamers, Nucleotide/chemistry/*pharmacology [MESH]
  • |Base Sequence [MESH]
  • |DNA Helicases/antagonists & inhibitors/*metabolism [MESH]
  • |G-Quadruplexes [MESH]
  • |Inhibitory Concentration 50 [MESH]
  • |Kinetics [MESH]
  • |Severe acute respiratory syndrome-related coronavirus/*enzymology [MESH]


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