Artificial receptors chemistry

Studies on molecular recognition by artificial receptors are thus one of the most important approaches to such characterization in relation to supramolecular chemistry [4]. Functional simulation of intracellular receptors in aqueous media has been actively carried out with attention to various noncovalent host-guest interactions, such as hydrophobic, electrostatic, hydrogen-bonding, charge-transfer, and van der Waals modes [5-10]. On the other hand, molecular recognition by artificial cell-surface receptors embedded in supramolecular assemblies has been scarcely studied up to the present time, except for channel-linked receptors [11-13]. 

Receptor chemistry, the chemistry of artificial receptor molecules, represents a generalized coordination chemistry, not limited to transition-metal ions but extending to all types of substrates cationic, anionic, or neutral species of organic, inorganic, or biological nature [1.13]. 

In summary, our approach of using cyclopeptides with natural amino acids and 3-aminobenzoic acid subunits for the development of macrocydic receptors has afforded remarkably efficient hosts. The cation affinity of 4b, for example, exceeds that of many calixarene derivatives. Even more interesting is the high anion affinity of 5 in aqueous solution. By introdudng additional functional groups such as car-boxylates to the periphery of the cavity, we recently also obtained cydopeptides that interact with neutral substrates, for example, carbohydrates [25]. Our peptides therefore represent a versatile dass of artificial receptor that should prove useful in supramolecular and bioorganic chemistry. 

Screening the encoded library produced interesting structures to build an SAR and to design focused libraries of binders for the artificial receptor, but some limitations of these linkers for applications different from peptide chemistry are clearly evident. The carbonate bond connecting the electrophone tag and the photocleavable linker (Figure 9.8) is sensitive to many organic reaction conditions, and the carboxylate requires an amino- or hydroxy function to be linked to the resin after each synthetic step to be encoded. 

Li, S., Sun, L., Chung, Y, and Weber, S. G, Artificial receptor-facilitated sohd-phase microextraction of barbiturates. Analytical Chemistry, 71, 2146,1999. 

Peptides composed of various coded and noncoded amino acid residues self-assemble to form various types of supramolecular architectures, including supramolecular helices and sheets, nanotubes, nanorods, nanovesicles, and nanofibers. The higher-order self-assembly of supramolecular (3-sheets or supramolecular helices composed of short synthetic acyclic peptides leads to the formation of amyloid-like fibrils. Synthetic cyclic peptides were used in supramolecular chemistry as molecular scaffolding for artificial receptors, so as to host various chiral and achiral ions and other small neutral substrates. Cyclic peptides also self-assemble like their acyclic counterparts to form supramolecular structures, including hollow nanotubes. Self-assembling cyclic peptides can be served as artificial ion channels, and some of them exhibit potential antimicrobial activities against drug-resistant bacteria. 

Artificial receptor design is an Important aspect of supramolecular chemistry. Synthetic cyclic peptides were... 

Galan, A. Andreu. D. Echavarren, A.M. Prados, P. de Mendoza. J. A receptor for enantioselective recognition of phenylalanine and triptophan under neutral conditions. J. Am. Chem. Soc. 1992. 115. 7037-7038. de Mendoza, J. Gago, F. Molecular Recognition of Dinucleotides and Amino Acids by Artificial Receptors Containing a Byciclic Guanidinium Subunit. In Computational Approches in Supramolecular Chemistry, Wipff, G., Ed. Kluwer Dordrecht, 1994 79-99. 

This bioorganometallic chemistry is envisioned to provide not only a pep-tidomimetic basis for protein folding, but also pharmacologically useful compounds, artificial receptors, asymmetric catalysts, and new materials with functional properties. 

The compleat coordination chemistry exists today because all of the binding interactions that yield distinct molecular species, Le., coordination entities, by the union of two or more lesser molecular species, Le., complex formations, can now be included within the expanded field. Quoting from Lehn (3), "the chemistry of artificial receptor molecules may be considered a generalized coordination chemistry, not limited to transition metal ions but extending to all types of substrates (receptees) cationic, anionic, or neutral species of organic, inorganic, or biological nature. ... 

The chemistry of artificial receptor molecules has produced a great variety of supramolecular structures displaying molecular recognition processes. As a chemistry of the intermolecular bond it has contributed to the fundamental understanding of the elementary interactions on which recognition is based. As a design of efficient and selective receptors for substrates of numerous types it has led to the synthesis of many new molecules and made available a wealth of new properties. 

I should like to come back to Professor Luisi s question regarding the contribution made by organic receptor chemistry to the understanding of biological receptors. I feel that much depends on the question asked if the question is how, then one should study the biological material itself if the question is why, then the chemistry of artificial receptors should be studied not only for its own sake but also because it provides the elements for understanding the basis of binding and selectivity. 

It is also important to establish that the chemistry of molecular bioprobes is not a sub-discipline of molecular recognition [i.e. host-guest chemistry [4] (Fig. 7.1) in which a guest molecule binds in an artificial receptor site (the host ) which through selective interactions provides the recognition effect] rather, it is an application of molecular recognition. 

The lock and key principle [1,2] can be regarded as the central principle for molecular recognition in Nature [3]. Supramolecular chemistry mimics Nature e.g. by using artificial receptors for selective recognition [4]. It is fair to say that molecular recognition by synthetic receptors in solution has reached a high level... 

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