Phosphorylation of Oligopeptides: Design of Ultra-Hydrophilic Zwitterionic Peptides for Anti-Fouling Detection of Nucleic Acids in Saliva

Key Words:Ultra-Hydrophilic Zwitterionic Peptides;Anti-Fouling; Nucleic Acids detection

Abstract:Theconstruction of low-fouling biosensors for assaying biomarkersin complex biological samples remains a challenge, and the key limitationis the lack of effective anti-fouling materials. Inspired by the biomimeticprocess of protein phosphorylation, we herein designed a new phosphorylatedpeptide modified with the dihydrogen phosphate (-PO4H2) group, which significantly increased the hydrophilicityand anti-fouling capability of the peptide when compared with naturaland normal peptides. Molecular simulation (MS) illustrated that, comparedwith the -COOH and -NH2 groups, the -PO4H2 group formed the most numbers of hydrogen bondsand stronger hydrogen bonds with water molecules. As a result, thePO(4)H(2)-oligopeptide was proved by MS to be ableto attract the greatest number of water molecules, so as to form acompact layer of H2O to resist further adsorption of nonspecificbiomolecules. The modification of electrodes with the designed PO4H2-oligopeptides, in addition to the adoption ofneutral peptide nucleic acids (PNAs) as the sensing probes, ensuredthe fabrication of anti-fouling electrochemical biosensors capableof detecting nucleic acids in complex saliva. The constructed anti-foulingbiosensor was able to detect the nucleic acid of the severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) in undiluted saliva,with a wide linear response range (0.01 pM-0.01 & mu;M) anda low limit of detection (LOD) of 3.4 fM (S/N = 3). The phosphorylationof oligopeptides offers an effective strategy to designing ultra-hydrophilicpeptides suitable for the construction of promising anti-biofoulingbiosensors and bioelectronics.

Volume:95

Issue:29

Translation or Not:no