Streptomycin aptamer

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Timeline

1998

The aptamer was isolated for the first time[1]

2003

The first discovery of the streptomycin aptamer structure was made[2]

2006

Streptomycin aptamer was found to have clinical applications and also underwent drug trials[3]

2007

The first label-free modified RNA-aptasensor for the detection of small molecules in biological samples was presented[4]

2016

The stability of an aptamer, which was formed by two RNA strands and binds the antibiotic streptomycin[11]

2018

Rapid detection of streptomycin using POCT method modeled on streptomycin aptamer[12]

2019

The unfolding behavior of a streptomycin-binding ribonucleic acid (RNA) aptamer under application of forced in shear geometry[13]

2023

Truncated STR aptamers yield higher affinity S03 aptamers and can be used to detect STR recognition elements[14]

2023

The STR interacts with aptamer through forming stable hydrogen bonds[15]

Description

In 1998, Schroeder, R. et al. used in vitro selection techniques to isolate aptamers with high-affinity binding sites for Streptomycin. In 2003, Ellington, A. D et al. determined the tertiary structure of the aptamer for the first time. In 2007, Schroeder, R et al. introduced a label free modified RNA aptasensor for detecting small molecules in biological samples[1,2,4].



SELEX

Starting with a pool of 1015 different DNA molecules, in vitro selection procedures were carried out to select RNAs with a high affinity for streptomycin. Affinity chromatography was performed using dihydrostreptomycin coupled to sepharose. RNA from the starting pool was applied to the dihydrostreptomycin column and specifically eluted. RNAs from the three final pools were reverse-transcribed, PCR amplified, cloned, and subjected to sequence analysis. Among the 99 clones sequenced (33 from each selection procedure), 43 were unique[1].

Detailed information are accessible on SELEX page.



Structure

2D representation

In 2003, Ellington, A. D et al. obtained the crystallographic structure of a streptomycin aptamer through X-ray diffraction techniques, and detailed the molecular recognition principles after analyzing the structural data. The RNA aptamer is characterised by an L-shaped architecture that forms a distinct binding pocket for streptomycin, as illustrated in the subsequent diagrams. Here we utilized RiboDraw to complete the figure, based the 3D structure information[2].

Chain A: 5'-GGAUCGCAUUUGGACUUCUGCC-3'
Chain B: 5'-CGGCACCACGGUCGGAUC-3'

drawing

3D visualisation

Ellington, A. D et al. determined the structures of complexes formed by the Streptomycin RNA aptamer at high resolution using X-ray crystallography. The structure of the Streptomycin RNA-aptamer complex was refined to a high resolution of 2.9 Å. The PDB ID for this structure is 1NTA[2].

Additional available structures that have been solved and detailed information are accessible on Structures page.

(Clicking the "Settings/Controls info" to turn Spin off)      

drawing PDBe Molstar




Binding pocket

Left: Surface representation of the binding pocket of the aptamer generated from PDB ID: 1NTA by X-ray. Streptomycin (shown in sticks) is labeled in magenta. Right: The hydrogen bonds of binding sites of the aptamer bound with streptomycin[2].

drawing drawing


Ligand information

SELEX ligand

The RNA aptamers, specifically those containing motif 1 and motif 2, were selected through in vitro selection procedures to bind streptomycin with high affinity and specificity. The binding affinity of these RNA aptamers was demonstrated using affinity chromatography. In this experiment, RNAs containing motifs 1 and motif 2 were subjected to dihydrostreptomycin-coupled sepharose beads, and the binding of streptomycin to the RNA aptamers was assessed by eluting the RNA with varying concentrations of streptomycin and bluensomycin. The elution profiles showed that the RNA containing motif 1 could be specifically eluted with 1 μM streptomycin, but not with 1 mM bluensomycin, indicating a high affinity for streptomycin and strong discrimination against bluensomycin. In subsequent research, the RNA in the crystal structure of the streptomycin aptamer complex was motif 1[1].

drawing

Structure ligand

Streptomycin is an aminoglycoside antibiotic indicated to treat multi-drug resistant mycobacterium tuberculosis and various non-tuberculosis infections.-----From Drugbank

PubChem CID: a unique identifier for substances in the PubChem database.

CAS number: a global registry number for chemical substances.

Drugbank: a comprehensive database with detailed information on drugs and drug targets.

Name PubChem CID Molecular Formula Molecular Weight CAS Solubility Drugbank ID
Streptomycin 19649 C21H39N7O12 581.6 g/mol 57-92-1 40 g/L (at 20 °C) DB01082
drawing drawing

Similar compound(s)

We screened the compounds with great similarity to streptomycin 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.

ZINC ID: a compound identifier used by the ZINC database, one of the largest repositories for virtual screening of drug-like molecules.

PubChem CID: a unique identifier for substances in the PubChem database.

CAS number: a global registry number for chemical substances.

ZINC ID Name CAS Pubchem CID Structure
ZINC8214681 Streptomycin 57-92-1 19649 drawing
ZINC36176697 2-[(1S,2R,3R,4R,5S,6S)-3-(diaminomethylideneamino)-4-[(2R,3S,4S,5S)-3-[(2R,3R,4S,5S,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine NA 93190235 drawing
ZINC36176688 2-[(1S,2R,3R,4R,5S,6S)-3-(diaminomethylideneamino)-4-[(2R,3S,4R,5S)-3-[(2R,3R,4S,5S,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine NA 93190230 drawing
ZINC8101190 2-[(1S,2R,3R,4R,5S,6S)-3-(diaminomethylideneamino)-4-[(2R,3S,4R,5R)-3-[(2R,3R,4S,5S,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine NA 92328111 drawing
ZINC1078030477 2-[(1R,2S,3S,4S,5S,6R)-3-(diaminomethylideneamino)-4-[(2S,3S,4R,5R)-3-[(2S,3S,4S,5S,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine NA 44120113 drawing
ZINC8214760 2-[(1R,2R,3S,4R,5R,6S)-3-(diaminomethylideneamino)-4-[(2R,3S,4R,5S)-3-[(2S,3S,4S,5R,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine NA 2735213 drawing
ZINC253487932 2-[(1R,2S,3S,4S,5R,6R)-3-(diaminomethylideneamino)-4-[(2R,3S,4R,5R)-3-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine NA 124894813 drawing
ZINC253487934 2-[(1R,2S,3S,4S,5R,6R)-3-(diaminomethylideneamino)-4-[(2R,3S,4R,5R)-3-[(2S,3S,4R,5R,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine NA 124894815 drawing


References

[1] In vitro selection and characterization of streptomycin-binding RNAs: recognition discrimination between antibiotics.
Wallace, S. T., & Schroeder, R.
RNA (New York, N.Y.), 4(1), 112–123. (1998)
[2] Encapsulating streptomycin within a small 40-mer RNA.
Tereshko, V., Skripkin, E., & Patel, D. J.
Chemistry & biology, 10(2), 175–187. (2003)
[3] Aptamer therapeutics advance.
Lee, J. F., Stovall, G. M., & Ellington, A. D.
Current opinion in chemical biology, 10(3), 282–289. (2006)
[4] Modified-RNA aptamer-based sensor for competitive impedimetric assay of neomycin B.
de-los-Santos-Alvarez, N., Lobo-Castañón, M. J., Miranda-Ordieres, A. J., & Tuñón-Blanco, P.
Journal of the American Chemical Society, 129(13), 3808–3809 (2007)
[5] Isolation of small RNA-binding proteins from E. coli: evidence for frequent interaction of RNAs with RNA polymerase.
Windbichler, N., von Pelchrzim, F., Mayer, O., Csaszar, E., & Schroeder, R.
RNA biology, 5(1), 30–40. (2008)
[6] Aptamers biosensors for pharmaceutical compounds.
Tombelli, S., & Mascini, M.
Combinatorial chemistry & high throughput screening, 13(7), 641–649. (2010)
[7] The tuberculosis drug streptomycin as a potential cancer therapeutic: inhibition of miR-21 function by directly targeting its precursor.
Bose, D., Jayaraj, G., Suryawanshi, H., Agarwala, P., Pore, S. K., Banerjee, R., & Maiti, S.
Angewandte Chemie (International ed. in English), 51(4), 1019–1023. (2012)
[8] Toggled RNA aptamers against aminoglycosides allowing facile detection of antibiotics using gold nanoparticle assays.
Derbyshire, N., White, S. J., Bunka, D. H., Song, L., Stead, S., Tarbin, J., Sharman, M., Zhou, D., & Stockley, P. G.
Analytical chemistry, 84(15), 6595–6602 (2012)
[9] Selection and identification of streptomycin-specific single-stranded DNA aptamers and the application in the detection of streptomycin in honey.
Zhou, N., Wang, J., Zhang, J., Li, C., Tian, Y., & Wang, J.
Talanta, 108, 109–116. (2013)
[10] Tombusvirus Y-shaped translational enhancer forms a complex with eIF4F and can be functionally replaced by heterologous translational enhancers.
Nicholson, B. L., Zaslaver, O., Mayberry, L. K., Browning, K. S., & White, K. A.
Journal of virology, 87(3), 1872–1883. (2013)
[11] Stability of a Split Streptomycin Binding Aptamer.
Nick, T. A., de Oliveira, T. E., Pilat, D. W., Spenkuch, F., Butt, H. J., Helm, M., Netz, P. A., & Berger, R.
The journal of physical chemistry. B, 120(27), 6479–6489. (2016)
[12] Point-of-care testing for streptomycin based on aptamer recognizing and digital image colorimetry by smartphone.
Lin, B., Yu, Y., Cao, Y., Guo, M., Zhu, D., Dai, J., & Zheng, M.
Biosensors & bioelectronics, 100, 482–489. (2018)
[13] Single molecule force spectroscopy of a streptomycin-binding RNA aptamer: An out-of-equilibrium molecular dynamics study.
Baptista, L. A., & Netz, P. A.
The Journal of chemical physics, 151(19), 195102. (2019)
[14] Truncated affinity-improved aptamer for selective and sensitive detection of streptomycin in dairy products with label-free electrochemical aptasensor.
Yuanyuan Hui, Ding Yang, Weizhe Wang, Yingying Liu, Chao He, Bini Wang
Journal of Food Composition and Analysis (2023)
[15] Three-dimensional modeling of streptomycin binding single-stranded DNA for aptamer-based biosensors, a molecular dynamics simulation approach.
Nosrati, M., & Roushani, M.
Journal of biomolecular structure & dynamics, 41(8), 3430–3439. (2023)