9th April 2019

Changes in the glycosylation pattern of cell surface and secreted glycoproteins are common in malignant transformations and cancer progression, (1).  Prostate-specific antigen (PSA), is a glycoprotein enzyme secreted by the prostate gland that is often used for diagnosing and predicting progression of prostate cancer in men.  Recent advances in the field of glycobiology have demonstrated that during tumorigenesis subtle changes in the glycan structure of PSA occur which may allow to distinguish PSA from normal and tumor cells. (2,3).

The main goal of the research was to select ssDNA aptamers through the use of counter-selections targeting the non-glycosylated protein, thus removing from the selection pool the oligonucleotides that recognize the protein by positions different from the glycosylation site. These aptamers were then challenged as signaling receptors in a sandwich electrochemical aptasensor for the detection of PSA in serial dilutions of PSA and clinical samples.

Additional experiments also showed that the selected aptamers could detect similarly glycosylated lipocalin-2 (NGAL), indicating specificity for the glycan structure that could become general reagents for protein carbohydrate side chains. Using the sandwich assay approach with anti-PSA aptamer secures the selectivity of the assay against glycoproteins other than PSA. The proposed aptasensor could provide an alternative approach for the detection of PSA, with potential to improve clinical outcomes of PSA tests and to reduce the number of unnecessary biopsies for the diagnosis of prostate cancer.

Díaz-Fernández, A., Miranda-Castro, R., de-los-Santos-Álvarez, Fernández, E. (2019).  Focusing aptamer selection on the glycan structure of prostate-specific antigen: Toward more specific detection of prostate cancer. Biosens Bioelectron. 2019 Mar 1;128:83-90

https://www.sciencedirect.com/science/article/pii/S0956566318310030

References:

  1. Munkley, J., Elliot, D.J., 2016. Oncotarget 7, 35478-35489.
  2. Saldova, R., Fan, Y., Fitzpatrick J.M., Watson R.W.G., Rudd, P.M., 2011.Glycobiology 21, 195-205.
  3. Tabarés, G., Radcliffe, C.M., Barrabés, S., Ramírez, M., Aleixandre, R.N., Hoesel, W., Dwek, R.A., Rudd, P.M., Peracaula, R., de Llorens, R., 2006. Glycobiology 16, 132-145

Aptamer Group has successfully selected aptamers to modified targets with only a single amino acid difference, if you would like more information on aptamers for your glycosylation or other post translational modification research contact us using the form below:

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