Analysis of the evolution of the thrombin-inhibiting DNA aptamers using a genetic algorithm.
We previously identified a thrombin-inhibiting DNA aptamer that was presumed to form a G-quartet structure with a duplex. To investigate the importance of the sequences in the duplex region and to obtain aptamers with higher inhibitory activities, we randomized the sequences of the duplex region of this aptamer and carried out selection based on inhibitory activity using a genetic algorithm. This method consisted of selection via an inhibition assay, crossover, and mutation in silico. After two cycles, we obtained ligands with greater inhibitory activities than that of the original aptamer. In addition, the duplex sequences were found to contribute to the inhibitory activities of aptamers.
Ikebukuro
Kazunori
K
Department of Life Science and Biotechnology, Tokyo University of Agriculture and Technology, Naka-cho, Koganei, Tokyo, Japan, ikebu@cc.tuat.ac.jp
Yoshida
Wataru
W
Noma
Takahisa
T
Sode
Koji
K
D000465:Algorithms; D052157:Aptamers, Nucleotide; D001709:Biotechnology / Q000379:methods*; D002627:Chemistry, Physical / Q000379:methods; D004247:DNA / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008957:Models, Genetic; D008968:Molecular Conformation; D009154:Mutation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry
D052157:Aptamers, Nucleotide; D008024:Ligands; D012313:RNA; D005340:Fibrinogen; D004247:DNA; D013917:Thrombin