Dynamic combinatorial libraries receptor

Figure 8.53 Dynamic combinatorial libraries receptor-driven ligand library selection (top) and ligand-driven receptor library selection (bottom).

Scheme 40 Synthesis of receptor 80-S-S-80 from a dynamic combinatorial library based on 80-SH and 81-SH. The receptor is amplified in the presence of a tripeptide template...

Otto S, Severin K (2007) Dynamic Combinatorial Libraries for the Development of Synthetic Receptors and Sensors. 277 267-288... 

Ludlow, R. F. Otto, S. Two-vial, LC-MS identification of ephedrine receptors from a solution-phase dynamic combinatorial library of over 9000 components. J. Am. Chem. Soc. 2008,130, 12218-12219. 

Corbett, P. T Sanders, J. K. M. Otto, S. Exploring the relation between amplification and binding in dynamic combinatorial libraries of macrocyclic synthetic receptors in water. Chem. Eur. J. 2008,14, 2153-2166. 

Voshell SM, Lee SJ, Gagne MR (2006) The discovery of an enantioselective receptor for (—)-adenosine from a racemic dynamic combinatorial library. J Am Chem Soc 128 12422-12423... 

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It is worth noting that this process could in principle lead to dynamic combinatorial libraries of products since the type of bond that brings together the different components in the reaction is a reversible one (namely imine formation). In fact, the initial mixture of products observed by the authors has been postulated to be a mixture of different-sized macrocycles and linear species (from which one of them is amplified upon addition of terephthalate). More detailed studies would be needed to determine whether this system indeed leads to the formation of a DCL of receptors (see Sect. 4 for examples of anion-directed DCLs). 

The use of anions as templating agents is discussed by Vilar. The chapter starts with a general overview of the area and a discussion of the applications of anion templates in organic and coordination chemistry. The second part of the chapter deals with examples where anions are employed as templates in dynamic combinatorial libraries. This approach promises to provide an efficient route for the synthesis of better and more selective anion receptors. The last chapter by Ewen and Steinke also deals with the use of anions as templates but in this case in the context of molecular imprinted polymers. The first half of the chapter provides an introduction into molecularly imprinted polymers and this is followed by a detailed discussion of examples where anionic species have been used to imprint this class of polymeric materials. 

Cousins. G.R.L. Furlan. R.L.E. Kg. Y.-F. Redman. J.E. Sanders, J.K.M. Identification and isolation of a receptor for N-methyl alkylammonium salts Molecular amplification in a pseudo-peptide dynamic combinatorial library. Angew. Chem. Int. Ed. 2001. 40. 423-428. 

Fig. 5 Mixing di- and tripyridyl ligands (7-11) with Pd(en) produces a diverse dynamic combinatorial library of cyclic and cage coordination compounds. Exposure of this library to sodium trichloroacetate (12) results in the amplification of a new receptor. (Adapted from Ref. [17].)...

The basic concepts of selection experiments with dynamic combinatorial libraries (DCLs) were articulated more than 10 years ago (see Chapter 1). Since then, a number of applications have emerged. This includes the discovery new enzyme inhibitors, receptors, and catalysts, as well as the synthesis of novel materials such as responsive gels and polymers (see Chapters 2-5). A recent addition to the list of applications is the utilization of dynamic combinatorial chemistry (DCC) for analyhcal purposes. This chapter summarizes the main ideas and results in this area. 

This rationale led Severin et alP to construct an array consisting of CuCh, NiCh, and three UV-active chro-mophores, resulting in six metal-indicator combinations to comprise a dynamic combinatorial library. A dynamic combinatorial library is an array of differential sensors that are simultaneously present in one solution, under thermodynamic control, such that this one solution can provide multiple signals from the composite interactions of an analyte with all the sensors in solution. They found that this simple dynamic combinatorial library of receptors was able to successfully discriminate two angiotensin peptides (angiotensin I and angiotensin II) and mixtures of these two peptides. 

Dynamic combinatorial chemistry (DCC) has proven extremely useful in creating complex mixtures of interchanging compounds termed dynamic combinatorial libraries (DCL). Key to the formation of such DCLs is a reversible chemical process that allows the library members to interconvert. The formation of imines from aldehydes and amines is a prominent example for the creation of a DCL. Since the overall distribution of compounds is under thermodynamic control, external stimuli can be used to bias the DCL toward a specific member of the library. This approach has been exploited successfully in the search of potent receptors for molecules of pharmacological interest, the creation of supramolecular assemblies, and ligands for biomacromolecules. ... 

Dynamic combinatorial chemistry (DCC) is marvelously effective at discovering receptors for a broad array of analytes. The nature of the internal competition experiment ensures (normally) that the most effective binder for the analyte of interest is amplified for subsequent identification and characterization. In the context of a host-guest assembly, the issue of stereochemistry can be manifested in a number of scenarios. These include various permutations of chiral or achiral guests, along with achiral, enan-tiopure, or racemic dynamic library components. 

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