Skip to main content

Advertisement

Log in

Polymers imprinted with three REG1B peptides for electrochemical determination of Regenerating Protein 1B, a urinary biomarker for pancreatic ductal adenocarcinoma

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract

Three peptides (each containing 13–18 amino acids) were synthesized and used as templates for molecular imprinting and epitope recognition of the Regenerating Protein 1B (REG1B), which is one of the urinary biomarkers for pancreatic ductal adenocarcinoma (PDAC). Poly(ethylene-co-vinyl alcohol)s were employed as the host for molecular imprinting of the peptides. Following their preparation, the molecularly imprinted polymers (MIP) were examined by cyclic voltammetry. The electrochemical responses of a screen-printed gold substrate coated with the MIP were measured at a working voltage of 300 mV (vs. Ag/AgCl); the entire protein and the peptides gave similar responses at concentrations of <1.0 pg⋅mL−1, with detection limits as low as 0.1 pg⋅mL−1. Urine samples from healthy and PDAC patients were then analyzed by using this modified gold electrode, and the results are in agreement with data obtained with ELISA.

Three peptides (each containing 13–18 amino acids) were synthesised and used as templates for imprinting and epitope recognition of Regenerating Protein 1B (REG1B), which is one of the urinary biomarkers for pancreatic ductal adenocarcinoma (PDAC).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ge Y, Turner APF (2008) Too large to fit? Recent developments in macromolecular imprinting. Trends Biotechnol 26(4):218–224

    Article  CAS  Google Scholar 

  2. Turner NW, Jeans CW, Brain KR, Allender CJ, Hlady V, Britt DW (2006) From 3D to 2D: a review of the molecular imprinting of proteins. Biotechnol Prog 22(6):1474–1489

    Article  CAS  Google Scholar 

  3. Rachkov A, Minoura N (2000) Recognition of oxytocin and oxytocin-related peptides in aqueous media using a molecularly imprinted polymer synthesized by the epitope approach. J Chromatogr A 889(1–2):111–118. doi:10.1016/S0021-9673(00)00568-9

    Article  CAS  Google Scholar 

  4. Rachkov A, Hu M, Bulgarevich E, Matsumoto T, Minoura N (2004) Molecularly imprinted polymers prepared in aqueous solution selective for [Sar1,Ala8]angiotensin II. Anal Chim Acta 504(1):191–197. doi:10.1016/S0003-2670(03)00764-5

    Article  CAS  Google Scholar 

  5. Tai D-F, Lin C-Y, Wu T-Z, Chen L-K (2005) Recognition of dengue virus protein using epitope-mediated molecularly imprinted film. Anal Chem 77(16):5140–5143. doi:10.1021/ac0504060

    Article  CAS  Google Scholar 

  6. Tai D-F, Lin Y-F (2008) Molecularly imprinted cavities template the macrocyclization of tetrapeptides. Chem Commun 43:5598–5600. doi:10.1039/B813439A

    Article  Google Scholar 

  7. Tai D-F, Jhang M-H, Chen G-Y, Wang S-C, Lu K-H, Lee Y-D, Liu H-T (2010) Epitope-cavities generated by molecularly imprinted films measure the coincident response to anthrax protective antigen and its segments. Anal Chem 82(6):2290–2293. doi:10.1021/ac9024158

    Article  CAS  Google Scholar 

  8. Tai D-F, Ho Y-F, Wu C-H, Lin T-C, Lu K-H, Lin K-S (2011) Artificial-epitope mapping for CK-MB assay. Analyst 136(11):2230–2233. doi:10.1039/C0AN00919A

    Article  CAS  Google Scholar 

  9. Bossi AM, Sharma PS, Montana L, Zoccatelli G, Laub O, Levi R (2012) Fingerprint-imprinted polymer: rational selection of peptide epitope templates for the determination of proteins by molecularly imprinted polymers. Anal Chem 84(9):4036–4041. doi:10.1021/ac203422r

    Article  CAS  Google Scholar 

  10. Yang Y-Q, He X-W, Wang Y-Z, Li W-Y, Zhang Y-K (2014) Epitope imprinted polymer coating CdTe quantum dots for specific recognition and direct fluorescent quantification of the target protein bovine serum albumin. Biosens Bioelectron 54:266–272. doi:10.1016/j.bios.2013.11.004

    Article  CAS  Google Scholar 

  11. Wang Y-Z, Li D-Y, He X-W, Li W-Y, Zhang Y-K (2015) Epitope imprinted polymer nanoparticles containing fluorescent quantum dots for specific recognition of human serum albumin. Microchim Acta 182(7–8):1465–1472. doi:10.1007/s00604-015-1464-1

    Article  CAS  Google Scholar 

  12. Zhao X-L, Li D-Y, He X-W, Li W-Y, Zhang Y-K (2014) An epitope imprinting method on the surface of magnetic nanoparticles for specific recognition of bovine serum album. J Mater Chem B 2(43):7575–7582. doi:10.1039/C4TB01381F

    Article  CAS  Google Scholar 

  13. Yang K, Li S, Liu J, Liu L, Zhang L, Zhang Y (2016) Multiepitope templates imprinted particles for the simultaneous capture of various target proteins. Anal Chem 88(11):5621–5625. doi:10.1021/acs.analchem.6b01247

    Article  CAS  Google Scholar 

  14. Piletsky SA, Turner APF (2002) Electrochemical sensors based on molecularly imprinted polymers. Electroanalysis 14(5):317–323. doi:10.1002/1521-4109(200203)14:5<317::aid-elan317>3.0.co;2-5

    Article  CAS  Google Scholar 

  15. Blanco-López MC, Lobo-Castañón MJ, Miranda-Ordieres AJ, Tuñón-Blanco P (2004) Electrochemical sensors based on molecularly imprinted polymers. TrAC Trends Anal Chem 23(1):36–48

    Article  Google Scholar 

  16. McCluskey A, Holdsworth CI, Bowyer MC (2007) Molecularly imprinted polymers (MIPs): sensing, an explosive new opportunity? Org Biomol Chem 5(20):3233–3244

    Article  CAS  Google Scholar 

  17. Prasada Rao T, Kala R (2008) Potentiometric transducer based biomimetic sensors for priority envirotoxic markers--an overview. Talanta 76(3):485–496

    Article  CAS  Google Scholar 

  18. Suryanarayanan V, Wu C-T, Ho K-C (2010) Molecularly imprinted electrochemical sensors. Electroanalysis 22(16):1795–1811. doi:10.1002/elan.200900616

    Article  CAS  Google Scholar 

  19. Salmi Z, Benmehdi H, Lamouri A, Decorse P, Jouini M, Yagci Y, Chehimi MM (2013) Preparation of MIP grafts for quercetin by tandem aryl diazonium surface chemistry and photopolymerization. Microchim Acta 180(15):1411–1419. doi:10.1007/s00604-013-0993-8

    Article  CAS  Google Scholar 

  20. Bates F, del Valle M (2015) Voltammetric sensor for theophylline using sol–gel immobilized molecularly imprinted polymer particles. Microchim Acta 182(5):933–942. doi:10.1007/s00604-014-1413-4

    Article  CAS  Google Scholar 

  21. Huang C-Y, O'Hare D, Chao IJ, Wei H-W, Liang Y-F, Liu B-D, Lee M-H, Lin H-Y (2015) Integrated potentiostat for electrochemical sensing of urinary 3-hydroxyanthranilic acid with molecularly imprinted poly(ethylene-co-vinyl alcohol). Biosens Bioelectron 67:208–213. doi:10.1016/j.bios.2014.08.018

    Article  CAS  Google Scholar 

  22. Li S, Liu C, Yin G, Luo J, Zhang Z, Xie Y (2016) Supramolecular imprinted electrochemical sensor for the neonicotinoid insecticide imidacloprid based on double amplification by Pt-in catalytic nanoparticles and a bromophenol blue doped molecularly imprinted film. Microchim Acta 183(12):3101–3109. doi:10.1007/s00604-016-1962-9

    Article  CAS  Google Scholar 

  23. Huang C-Y, Tsai T-C, Thomas JL, Lee M-H, Liu B-D, Lin H-Y (2009) Urinalysis with molecularly imprinted poly(ethylene-co-vinyl alcohol) potentiostat sensors. Biosens Bioelectron 24(8):2611–2617. doi:10.1016/j.bios.2009.01.016

    Article  CAS  Google Scholar 

  24. Lee M-H, Thomas JL, Chang Y-C, Tsai Y-S, Liu B-D, Lin H-Y (2016) Electrochemical sensing of nuclear matrix protein 22 in urine with molecularly imprinted poly(ethylene-co-vinyl alcohol) coated zinc oxide nanorod arrays for clinical studies of bladder cancer diagnosis. Biosens Bioelectron 79:789–795. doi:10.1016/j.bios.2016.01.005

    Article  Google Scholar 

  25. Navakul K, Warakulwit C, Yenchitsomanus P-t, Panya A, Lieberzeit PA, Sangma C., A novel method for dengue virus detection and antibody screening using a graphene-polymer based electrochemical biosensor. Nanomedicine: Nanotechnol, Biol Med. doi:10.1016/j.nano.2016.08.009

  26. Lee M-H, Thomas JL, Chen W-J, Li M-H, Shih C-P, Lin H-Y (2015a) Fabrication of bacteria-imprinted polymer coated electrodes for microbial fuel cells. ACS Sustain Chem Eng 3(6):1190–1196. doi:10.1021/acssuschemeng.5b00138

    Article  CAS  Google Scholar 

  27. Chen W-J, Lee M-H, Thomas JL, Lu P-H, Li M-H, Lin H-Y (2013) Microcontact imprinting of algae on poly(ethylene-co-vinyl alcohol) for biofuel cells. ACS Appl Mater Interfaces 5(21):11123–11128. doi:10.1021/am403313p

    Article  CAS  Google Scholar 

  28. Birnbaumer GM, Lieberzeit PA, Richter L, Schirhagl R, Milnera M, Dickert FL, Bailey A, Ertl P (2009) Detection of viruses with molecularly imprinted polymers integrated on a microfluidic biochip using contact-less dielectric microsensors. Lab Chip 9(24):3549–3556. doi:10.1039/B914738A

    Article  CAS  Google Scholar 

  29. Lee M-H, O'Hare D, Chen Y-L, Chang Y-C, Yang C-H, Liu B-D, Lin H-Y (2014) Molecularly imprinted electrochemical sensing of urinary melatonin in a microfluidic system. Biomicrofluidics 8(5):054115. doi:10.1063/1.4898152

    Article  Google Scholar 

  30. Cheng L-P, Young T-H, You W-M (1998) Formation of crystalline EVAL membranes by controlled mass transfer process in water–DMSO–EVAL copolymer systems. J Membr Sci 145(1):77–90. doi:10.1016/S0376-7388(98)00063-5

    Article  CAS  Google Scholar 

  31. Bertrand JA, Pignol D, Bernard JP, Verdier JM, Dagorn JC, Fontecilla-Camps JC (1996) Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation. EMBO J 15(11):2678–2684

    CAS  Google Scholar 

  32. Radon TP, Massat NJ, Jones R, Alrawashdeh W, Dumartin L, Ennis D, Duffy SW, Kocher HM, Pereira SP, Guarner L, Murta-Nascimento C, Real FX, Malats N, Neoptolemos J, Costello E, Greenhalf W, Lemoine NR, Crnogorac-Jurcevic T (2015) Identification of a three-biomarker panel in urine for early detection of pancreatic adenocarcinoma. Clin Cancer Res 21(15):3512–3521. doi:10.1158/1078-0432.ccr-14-2467

    Article  CAS  Google Scholar 

  33. Lavignac N, Brain KR, Allender CJ (2006) Concentration dependent atrazine–atrazine complex formation promotes selectivity in atrazine imprinted polymers. Biosens Bioelectron 22(1):138–144. doi:10.1016/j.bios.2006.03.017

    Article  CAS  Google Scholar 

  34. El-Sharif HF, Hawkins DM, Stevenson D, Reddy SM (2014) Determination of protein binding affinities within hydrogel-based molecularly imprinted polymers (HydroMIPs). Phys Chem Chem Phys 16(29):15483–15489. doi:10.1039/C4CP01798F

    Article  CAS  Google Scholar 

  35. Lakshmi D, Bossi A, Whitcombe MJ, Chianella I, Fowler SA, Subrahmanyam S, Piletska EV, Piletsky SA (2009) Electrochemical sensor for catechol and dopamine based on a catalytic molecularly imprinted polymer-conducting polymer hybrid recognition element. Anal Chem 81(9):3576–3584. doi:10.1021/ac802536p

    Article  CAS  Google Scholar 

  36. Lee M-H, Thomas JL, Li M-H, Shih C-P, Jan J-S, Lin H-Y (2015b) Recognition of Rhodobacter sphaeroides by microcontact-imprinted poly(ethylene-co-vinyl alcohol). Colloids Surf B: Biointerfaces 135:394–399. doi:10.1016/j.colsurfb.2015.07.074

    Article  CAS  Google Scholar 

  37. Lin H-Y, Ho M-S, Lee M-H (2009) Instant formation of molecularly imprinted poly(ethylene-co-vinyl alcohol)/quantum dot composite nanoparticles and their use in one-pot urinalysis. Biosens Bioelectron 25(3):579–586. doi:10.1016/j.bios.2009.03.039

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We appreciate financial supports from Ministry of Science and Technology of ROC under Contract nos. MOST 104-2220-E-390-001, MOST 104-2220-E-006-006, MOST 105-2918-I-214-001 and MOST105-2221-E-214-036-.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hung-Yin Lin.

Ethics declarations

The author(s) declare that they have no competing interests. The collection of urine samples was approved by the London Brent Research Ethics Committee (REC number 05/Q0408/65).

Electronic supplementary material

ESM 1

(DOC 900 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, MH., Thomas, J.L., Liao, CL. et al. Polymers imprinted with three REG1B peptides for electrochemical determination of Regenerating Protein 1B, a urinary biomarker for pancreatic ductal adenocarcinoma. Microchim Acta 184, 1773–1780 (2017). https://doi.org/10.1007/s00604-017-2169-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00604-017-2169-4

Keywords

Navigation