The anti-cocaine aptamer was fragmented into two nucleic acids, (1) and (2). The nucleic acid (1) was tethered at its 5'-end to aminoethyl nicotinamide adenine dinucleotide, amino-NAD(+), or to horseradish peroxidase, HRP. The nucleic acid (2) was functionalized at its 3'-end with alcohol dehydrogenase, AlcDH, or with glucose oxidase, GOx. In the presence of cocaine, the supramolecular NAD(+)/AlcDH/cocaine-aptamer complex is formed, and the biocatalytic oxidation of ethanol is activated. Similarly, in the presence of cocaine, the GOx/HRP/cocaine-aptamer complex is formed, and this activates the biocatalytic cascade where glucose is oxidized by GOx to yield gluconic acid and H2O2, and the resulting hydrogen peroxide activates the HRP-biocatatyzed oxidation of 2,2'azinobis-(3 -ethylbenzthiazoline-6-sulfonate), ABTS(2-). The systems may be considered as biomimetic prototypes for systems biology.