Codeine aptamer

Jun 10, 2024 • Zhizhong Lu, Ying Ao

Timeline

Description

In 2006, RNA aptamers that bind the opium alkaloid codeine were generated using an iterative in vitro selection process. Two highest binding aptamer sequences, FC5 and FC45 with Kd values of 2.50 and 4.00 μM, respectively, were extensively studied. Corresponding mini-aptamers for FC5 and FC45 were subsequently identified through the described direct coupling Biacore assays^[1].

SELEX

A slightly modified in vitro selection procedure was used to isolate codeine-binding RNA aptamers from a library of RNA molecules containing a 30 nt random region flanked by constant primer-binding sequences. Aptamers were selected on a codeine affinity column, which was made by immobilizing codeine to the epoxy-activated agarose through its hydroxyl group. To enhance the stringency of the selection process, the wash volume was increased incrementally from cycles 6 to 15. To increase the specificity of the selected pool, a counter-selection with a 5 mM morphine solution was performed at cycle 10 prior to elution with codeine. After cycle 15, the enriched pool was cloned and approximately 60 colonies were sequenced^[1].
Detailed information are accessible on SELEX page.

Structure

The 2D structure of the figures is based on the article by ribodraw tool to draw. FC5L is the truncated sequence of full-length FC5. FC45L is the truncated sequence of full-length FC45^[1].

FC5L aptamer: 5'-GGGACAGGGCUAGCAGUAGGAUUGGGUGAGGGGAUGUGCUG-3'
FC45L aptamer: 5'-GGGACAGGGCUAGCUUAGUGCUAUGUGAGAAAAGGGUGUGGGGG-3'

Ligand information

SELEX ligand

Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, Papaver somniferum. It is typically used to treat mild to moderate degrees of pain.-----From Wiki

Name	Molecular Formula	MW	CAS	Solubility	PubChem	Drug ID
Codeine	C18H21NO3	299.4 g/mol	76-57-3	less than 1 mg/mL (at 70 °F)	5284371	DB00318

Similar compound

We screened the compounds with great similarity to by using the ZINC database and showed some of the compounds' structure diagrams. For some CAS numbers not available, we will supplement them with Pubchem CID. For another compound, we used a similar compound query method from the PubChem database.

Zinc_id	Named	CAS	pubchem CID	Structure
ZINC2041330	Morphine	57-27-2	5288826
ZINC3875420	Nalorphine	62-67-9	5284595
ZINC103562135	Etorphine	14521-96-1	644209
ZINC403529	Nalmefene	55096-26-9	5284594
ZINC1319780	Buprenorphine	52485-79-7	644073
ZINC4097183	Heroin	561-27-3	5462328

References

[1] Codeine-binding RNA aptamers and rapid determination of their binding constants using a direct coupling surface plasmon resonance assay.
Win, M. N., Klein, J. S., & Smolke, C. D.
Nucleic acids research, 34(19), 5670–5682. (2006)
[2] Aptamer-based Nanosensors: Juglone as an Attached-Redox Molecule for Detection of Small Molecules.
Saberian, M., Hamzeiy, H., Aghanejad, A., & Asgari, D.
BioImpacts : BI, 1(1), 31–36. (2011)
[3] A label-free electrochemical biosensor based on a DNA aptamer against codeine.
Huang, L., Yang, X., Qi, C., Niu, X., Zhao, C., Zhao, X., Shangguan, D., & Yang, Y.
Analytica chimica acta, 787, 203–210. (2013)
[4] An aptamer folding-based sensory platform decorated with nanoparticles for simple cocaine testing.
Guler, E., Bozokalfa, G., Demir, B., Gumus, Z. P., Guler, B., Aldemir, E., Timur, S., & Coskunol, H.
Drug testing and analysis, 9(4), 578–587. (2017)
[5] Triplex-quadruplex structural scaffold: a new binding structure of aptamer.
Bing, T., Zheng, W., Zhang, X., Shen, L., Liu, X., Wang, F., Cui, J., Cao, Z., & Shangguan, D.
Scientific reports, 7(1), 15467. (2017)