Novel strategy for DNA aptamers inhibiting enzymatic activity using algorithm mimicking evolution.
We screened the DNA aptamer inhibiting thrombin with novel method using algorithm mimicking evolution. For screening, we first randomly designed and synthesized ten 15-mer oligonucleotides supposed to form G-quartet structure and then measured the inhibitory activity for thrombin. The aptamers showing the high activities were selected and we shuffled and mutated those sequences in silico to generate 10 new sequences of aptamers for next generation. After repeating 5 cycles, we successfully obtained the same aptamers reported previously showing high inhibitory activity. In addition, we added 8-mer oligonucleotides to the both 5' and 3' ends of the selected 15-mer aptamer and then repeated evolution in silico. After 2 cycles, we were able to obtain the aptamer showing better inhibitory activity than the 15-mer aptamer.
D000465:Algorithms; D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D019143:Evolution, Molecular
D000991:Antithrombins; D004791:Enzyme Inhibitors; D004247:DNA