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Scheme 1. Synthesis of the three−component EB−TAPB−TFP COF using EB, TAPB and TFP as linkers. Scheme 1. Synthesis of the three−component EB−TAPB−TFP COF using EB, TAPB and TFP as linkers. Crystals 2022, 12, x FOR PEER REVIEW 5 of 12
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The development of new techniques for the detection of microRNAs (miRNAs) is highly desirable. Herein, a new crystalline three-component covalent organic framework (COF) termed EB-TAPB-TFP COF was synthesized under solvothermal conditions utilizing 1,3,5-triformylphloroglucinol, 1,3,5-tris(4-aminophenyl)benzene and ethidium bromide as monomers. Int...
Citations
... 61 Xie et al. designed a covalent-organic framework nanosheet-based QCM sensor to detect miRNA but in this case the nanosheet was simply employed to enhance signal generation in a complex probe DNA system. 62 One major advantage of a QCM sensor is its sensitivity: detectable changes in adsorbed mass are of the order of one nanogram per cm 2 . The simplest model relating ∆f to m is the Sauerbrey equation, 63 which is used to calculate the mass of the adsorbate. ...
Peptides are important biomarkers for a range of diseases, however distinguishing different amino-acid sequences using artificial receptors remains a major challenge in biomedical sensing. Here we present a new approach to creating highly selective recognition surfaces using phage display biopanning against metal-organic nanosheets (MONs) and demonstrate their use as the next-generation of biomolecular recognition surfaces. Three MONs (ZIF-7, ZIF-7-NH2 and Hf-BTB-NH2) were chosen as initial targets to demonstrate how simple synthetic modifications can enhance selectivity towards specific amino acid sequences. Each MON system was added to a solution containing every possible combination of 7-residue peptides attached to bacteriophage hosts and the highest affinity binding peptides for each system was identified via successive biopanning rounds. In each case only a single peptide sequence was isolated (YNYRNLL – ZIF-7, NNWWAPA – ZIF-7-NH2 and FTVRDLS – Hf-BTB-NH2). This indicates that these MONs are highly selective, which is attributed to their 2D nanosheet structure. Zeta potential and contact angle measurements were conducted on each MON and combined with calculated properties for the peptide sequences and binding studies to provide insights into the relative importance of electrostatic, hydrophobic and co-ordination bonding interactions. A quartz crystal microbalance (QCM) was used to model phage binding and the Hf-BTB-NH2 MON coated QCM produced a 5-fold higher signal for FTVRDLS functionalised phage compared to phage with generic peptide sequences. Further studies focusing on Hf-BTB-NH2 confirmed that the VRDL sequence was highly conserved, and on-target binding exhibited equilibrium dissociation constants that are comparable to natural recognition materials. Surface plasmon resonance (SPR) studies indicated a 4600-fold higher equilibrium dissociation constant (KD) for FTVRDLS compared to those obtained for off-target sequences, comparable to those of antibodies (KD = 4 x10-10). We anticipate that the highly tunable nature of MONs will enhance our understanding of binding interactions and enable molecular recognition of biomedically important peptides.
The quest for the development of high-accuracy, point-of-care, and cost-effective testing platforms for SARS-CoV-2 infections is ongoing as current diagnostics rely on either assays based on costly yet accurate nucleic acid amplification tests (NAAT) or less selective and less sensitive but rapid and cost-effective antigen tests. As a potential solution, this work presents a fluorescence-based detection platform using a metal-organic framework (MOF) in an effective assay, demonstrating the potential of MOFs to recognize specific targets of the SARS-CoV-2 genome with high accuracy and rapid process turnaround time. As a highlight of this work, positive detection of SARS-CoV-2 is indicated by a visible color change of the MOF probe with ultrahigh detection selectivities down to single-base mismatch nucleotide sequences, thereby providing an alternative avenue for the development of innovative detection methods for diverse viral genomes.
