A biomimetic glycosylated peptide sensor with enhanced assaying accuracy in complex biofluids

The application of electrochemical biosensing platforms in complex biological matrices is hindered by the combined effects of biofouling and enzymatic degradation of receptive or supporting interfacial elements. Here, bioinspired by the vascular endothelial glycocalyx, we introduce a β-d-glucose (β-d-Glc) moiety at the C-terminus of sensor-integrated peptide sequences to markedly enhance peptide-water interactions, reduce nonspecific adsorption, and protect the peptide backbone from proteolytic cleavage. Integrated experimental and all-atom molecular dynamic (MD) numerical investigations demonstrate that incubations in clinical human serum are associated with much higher levels of resistance. Interfacial aptamer co-immobilization then supports highly effective specific target recognition. The so-generated glycosylated peptide (GP) sensors display high detection accuracy (compared to hospital standards) and promising clinical applicability, over and above that possible with analogous non-glycosylated peptide (non-GP) analogues. This work, then, establishes a new, versatile and highly-accessible strategy to support highly challenging and diagnostically-impactful molecular detection.