ac9b03813_si_001.pdf (890.94 kB)
Self-Assembled Monolayer Epitope Bridges for Molecular Imprinting and Cancer Biomarker Sensing
journal contribution
posted on 2020-03-13, 15:05 authored by Julia Drzazgowska, Bianca Schmid, Roderich D. Süssmuth, Zeynep AltintasThe research in biomedicine,
cell signaling, diagnostics, and biocatalysis
rely on selective protein binders that specifically capture a protein
in a complex medium for either preparative or analytical use. These
molecules are generally of biological origin and exposed to instability,
denaturation, high cost, and inherently low binding capability. Imprinted
polymers, serving as the artificial protein binders, demonstrate good
potential to overcome these drawbacks. In this study, a novel epitope
imprinting strategy is reported by employing double-cysteine-modified
peptides as the templates and adsorbing the templates on a gold surface
by means of forming self-assembled monolayer bridges, followed by
electropolymerization to create a polymer network. The imprinted surface
was initially designed to demonstrate specific affinity toward a short
peptide (i.e., the epitope) or a target protein (i.e., neuron specific enolase) in buffer. This surface was
subsequently used to measure the cancer biomarker in human serum that
allows detecting 12 times lower concentration than threshold level
of the biomarker. The molecular receptors exhibited a Kd < 65 pM for their respective target protein and low
cross-reactivity with four nonspecific molecules. As compared to current
strategies for the epitope imprinting, for example, through traditional,
vertically adsorbed, or histidine-modified peptides, such a molecularly
tunable system based on a surface-imprinting process may provide more
efficient sensing systems with desirable affinity, sensitivity, and
specificity in diagnostics applications.