Reversibly modified thermostable enzymes for dna synthesis...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 9/16 (2006.01) C12N 9/12 (2006.01) C12N 9/22 (2006.01) C12N 9/99 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2409775

The invention relates to a composition comprising a first modified thermostable enzyme ex- hibiting 3'exonuclease activity but essentially no DNA polymerase activity and a second modified thermostable enzyme exhibiting DNA polymerase activity, whereas the fidelity of an amplifica- tion process is enhanced by the use of the composition in an amplification process in comparison to the use of the single second enzyme in an amplification process and, whereas said first and said second modified thermostable enzyme is reversibly modified by an inhibiting agent which results in essentially complete inactivation of enzyme activity, wherein incubation of said first and said second modified thermostable enzyme in an aqueous buffer at alkaline pH at a temperature less than 25 °C for 20 minutes results in no significant increase in the activity of said first and said second modified thermostable enzyme, wherein incubation at a temperature greater than 50 °C in an aqueous buffer at alkaline pH results in at least tow-fold increase in enzyme activity in less than 20 minutes which allow formation of primer extension products.

La présente invention a pour objet une composition contenant une première enzyme thermostable modifiée ayant l'activité d'une 3'-exonucléase, mais pratiquement aucune activité d'une ADN polymérase, et une seconde enzyme thermostable modifiée ayant l'activité d'une ADN polymérase, la fidélité d'un procédé d'amplification étant accrue par l'utilisation de cette composition en comparaison de l'utilisation de la seconde enzyme uniquement dans un procédé d'amplification. Ladite première enzyme et ladite seconde enzyme sont réversiblement modifiées par un agent inhibiteur qui a pour effet l'inactivation pratiquement complète de l'activité enzymatique, l'incubation de ladite première enzyme et de ladite seconde enzyme thermostavles modifiées dans un tampon aqueux alcalin et à une température inférieure à 25 oC pendant 20 minutes ne conduit à aucune augmentation significative de l'activité de ladite première enzyme et de ladite seconde enzyme, l'incubation de ladite première enzyme et de ladite seconde enzyme dans un tampon aqueux alcalin et à une température supérieure à 50 oC résulte en une augmentation au moins double de l'activité enzymatique en moins de 20 minutes, permettant la formation de produits d'extension d'amorce.

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