A general approach to differential sensing using synthetic molecular receptors

Abstract

Differential sensing is continuing to develop as an alternative to traditional, selective chemosensing techniques. This technique takes a cue from how the human senses of taste and smell operate in order to obtain qualitative and even quantitative data on single analytes and mixtures. Whereas classical chemosensing techniques inspired by the 'lock-and-key' approach depend on the development of a selective receptor for a target analyte, pattern-based sensing depends on the development of an array of cross-reactive receptors, which produce a collection of responses upon the array's interaction with a target analyte. This review focuses on an approach to differential sensing that diversifies synthetic receptors to be used in an array via appending combinatorial peptidic arms, metal ions, and indicators to a core binding unit.

Figure 1

Representation of the library of synthetic molecular receptors diversified for array sensing. The core unit (gray cup), which may be preorganized by means of a metal ion chelation (colored marbles), binds analytes of the same compound class. Diversity, and therefore cross-reactivity, in the array is made possible by the use of various indicators (green and blue inverted cup) and covalently appended moieties such as peptide chains (series of shapes). The array shown is a minimum array composed of a core binding unit × 2 metal ions × 2 indicators × 2 peptidic chains.

Figure 2

(a) Receptor library, 1, used in the differentiation of ATP, GTP, and AMP. (b) Principal component analysis (PCA) score plot showing the separation of responses. (c) Receptor library, 2, used for the discrimination of some proteins. (d) PCA score plot of the response from the arrayed indicator uptake assay of the different proteins (red – lysozyme, green – elastin, blue – ovalbumin, fuschia – fetuin, teal – BSA). (e) Receptor library, 3, used for the discrimination of tripeptides and tripeptide mixtures. (f) PCA score plot of the response from the arrayed indicator uptake assay of the different peptides (light blue – HGT, pink – HKT, dark blue –HGT, yellow – GHT).

Figure 3

(a) Receptor library, 3^x, used in the discrimination of tachykinins and their analogues. (b) PCA score plot of response from α-neurokinin (HKTDSFVGLM-NH₂) (blue), substance P (RPKPQQFFGLM-NH₂) (light blue), and tachykinin analogues HKT (red), HKTD (green), and HET (violet). (c) Receptor library employed in the pattern based discriminaton of phosphorylated peptides. (d) Peptides and their phosphorylated versions analyzed. (e) LDA plots of the response of the analytes in b. (f) Structure of 5.

Figure 4

(a) Boronic acid- functionalized receptor library used for the differentiation of sugars. (b) LDA plot of kinetic profiles of the indicator uptake of the array of receptors incubated with the sugars: fructose (orange triangle), glucose (green triangle), maltitol (light blue circle), maltose (blue diamond), sucralose (pink circle), sucrose (red diamond). (c) Peptide sequences used for the differentiation of tannins and wines. (d) Schematic representation of the indicator displacement assay of tannins using the peptidic ensembles in the array. (e) PCA score plot of responses of the different flavonoids (a - 0.060 mM, b - 0.12 mM) in (c). (f) Structures of flavonoids tested to determine the discriminatory properties of peptidic sensing ensembles.