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Literature Review: Distinguishing glycosylation patterns in proteins for the early detection of cancer

7th May 2019

Glycosylation is a post-translational modification where a carbohydrate is added to a protein. Glycosylation of proteins serves a number of functions in a cell, including: improve protein folding, forming lipid anchors and cell-to-cell adhesion. While glycosylation of a protein can be vital for its function, any changes in the position or number of glycosylation sites can cause a change in the protein function and may therefore be indicators for an underlying issue.

One example where aptamers have been used to differentiate between glycosylation states of a protein is in the paper entitled Focusing aptamer selection on the glycan structure of Prostate-Specific Antigen: toward more specific detection of prostate cancer by Diaz-Fernandez et al.

In this paper the group used human Prostate-Specific Antigen (PSA), which is glycosylated, and negatively selected against recombinant PSA, which is not glycosylated. Following careful aptamer selection, they were able to identify an aptamer that could discriminate hPSA from rPSA. Following the successful selection of aptamer pairs, Diaz-Fernandez et al adapted the aptamers into an ELISA-like assay and a biosensor. Both of these assays showed significant discrimination between the targets in human serum.

This proof of concept work shows a promising result and how it can be adapted for use in a sandwich format biosensor capable of specifically detecting glycosylated proteins in serum.

By expanding this work to other glycan proteins, it would be possible to develop diagnostics for other conditions associated with post translational modifications; including the early detection of cancer.

At Aptamer Group, we also have processes for isolation of aptamers against closely related targets which have undergone post translational modification. These aptamers can be easily modified before use in flow cytometry and fluorescent microscopy, as well as biosensors.

Díaz-Fernández A, Miranda-Castro R, de-Los-Santos-Álvarez N, Rodríguez EF, Lobo-Castañón MJ. Biosens Bioelectron (2019). Focusing aptamer selection on the glycan structure of prostate-specific antigen: Toward more specific detection of prostate cancer. Biosensors and Bioelectronics. 2019 Mar 1;128:83-90

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