Combinatorial Design of a Sialic Acid-Imprinted Binding Site

Abstract

Aberrant glycosylation has been proven to correlate with various diseases including cancer. An important alteration in cancer progression is an increased level of sialylation, making sialic acid one of the key constituents in tumor-specific glycans and an interesting biomarker for a diversity of cancer types. Developing molecularly imprinted polymers (MIPs) with high affinity toward sialic acids is an important task that can help in early cancer diagnosis. In this work, the glycospecific MIPs are produced using cooperative covalent/noncovalent imprinting. We report here on the fundamental investigation of this termolecular imprinting approach. This comprises studies of the relative contribution of orthogonally interacting functional monomers and their synergetic behavior and the choice of different counterions on the molecular recognition properties for the sialylated targets. Combining three functional monomers targeting different functionalities on the template led to enhanced imprinting factors (IFs) and selectivities. This apparent cooperative effect was supported by 1 H NMR and fluorescence titrations of monomers with templates or template analogs. Moreover, highlighting the role of the template counterion use of tetrabutylammonium (TBA) salt of sialic acid resulted in better imprinting than that of sodium salts supported by both in solution interaction studies and in MIP rebinding experiments. The glycospecific MIPs display high affinity for sialylated targets, with an overall low binding of other nontarget saccharides.

Improved selectivity of molecularly imprinted polymers based on the synergistic action of hydrogen bond and electrostatic interaction

“…The interaction changes the electron cloud density of the hydrogen atom when the carboxyl being a hydrogen bond donor 26,27 . The chemical shift of the amino on FM2 is 1.8843 ppm, after FM2 interacts with DFC, the chemical shift changes to 1.8738 ppm, which may be caused by the electrostatic interaction between the amino and the carboxyl of DFC 28 . When the two different kinds of functional monomers act with DFC at the same time, the changes of the above two chemical shifts are retained.…”

“…26,27 The chemical shift of the amino on FM2 is 1.8843 ppm, after FM2 interacts with DFC, the chemical shift changes to 1.8738 ppm, which may be caused by the electrostatic interaction between the amino and the carboxyl of DFC. 28 When the two different kinds of functional monomers act with DFC at the same time, the changes of the above two chemical shifts are retained. It effectively supports the existence of synergies between two different interactions.…”

Selective Sensing of Epinephrine by Phenylboronic Acid Tethered Carbon Dot

“…All these biomolecules have a 'diol' moiety that can covalently link with PBA appended CD through boronatediol linkage. [29][30][31][32] Subsequently, CD1-PBAs could detect such biomolecules through changes in its spectroscopic behavior.…”

Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores—Assessment of the Binding Behavior to Cancer Cells

“…Being of non-biological origin, engineered MIPs are extremely robust, resist denaturing solvents, are stable at high temperatures, and can be reproduced at a low cost [11]. Indeed, MIPs have been successfully applied as artificial recognition elements in targeting glycans such as SA and glycosaminoglycans (GAGs) [10,[12][13][14][15][16]. We, and others, used monosaccharide SA as a template and developed core-shell SA-imprinted particles with a defined size, which can be further applied as imaging agents for cell surface glycans [17][18][19][20][21][22].…”