Chiral target-specific

The chirality of DNA was applied to selective separation. A DNA aptamer as a new target-specific chiral selector for HPLC was investigated by Michaud et al. [119,120]. They showed that a tailor-made chiral stationary phase based on a DNA aptamer with known stereospecific binding for the D-enantiomer of the oligopeptide, arginine-vasopressin, exhibits enantioselectivity between the d- and L-peptides. This DNA-based target-specific aptamer chiral stationary phase provides a powerful tool for the resolution of small (bioactive) molecule enantiomers. 

The presence of chiral centres in the natural products provides for higher affinity and target specificity, and clearly differentiates them from non-natural compounds. Henkel et al.16 found a different numerical value for this parameter but the trend was identical. 

An emerging area of modem enantioselective analytics is the development of dedicated, target-specific molecular tools that meet the criteria of being robust, high throughput, and specific [105]. Important groups of such tools constitute chiral artificial sensors and receptors as well as polymer-based chiral materials, such as... 

E. Immobilized DNA aptamers as target-specific chiral stationary phases for resolution of nucleoside and amino acid derivative enantiomers, Anal. Chem., 2004, 76, 1015-1020. 

Michaud, M., Jourdan, E., Ravelet, C., Villet, A., Ravel, A., Grosset, C., Peyrin, E. (2004). Immobilized DNA aptamers as target-specific chiral stationary phases for resolution of nucleoside and amino acid derivative enantiomers. Anal Chem 76, 1015-1020. 

Nncleic acid aptamers were first exploited by our group for use in target-specific chiral separations by EC. Immobilized DNA, RNA and l-RNA (spiegelmer) oligonucleotides have been nsed snccessfnlly for the separation of enantiomers of various compounds. Table 10.1 snmmarizes the aptamer-based CSPs reported to date. 

TABLE 10.1 Aptamers Used as Target-Specific Chiral Stationary Phases for LC Enantiomeric Separation... 

The first example of aptamer-based target-specific chromatographic chiral separation has been reported using an antioligopeptide DNA aptamer. The enantiomers of arginine-vasopressin were separated using an inunobilized 55-base DNA aptamer (Michaud et al., 2003) known to bind the D-enantiomer of the oligopeptide stereopecifically (Williams et al., 1997). The influence of... 

Another major drawback of aptamers is related to the too-high target specificity obtained when using the SELEX procedure. For a broad application in the chiral separation field, such a high specificity is assumed to be of poor practical interest. 

Macrocyclic glycopeptides are antibiotics produced by different bacterial strains (Table 1) to inhibit the growth of bacterial competitors. These molecules can target specifically the terminal o-Ala-o-Ala sequence of a protein essential to Grampositive cell wall building [1]. Not surprisingly, these molecules were found to be excellent chiral selectors in discriminating between amino acid enantiomers [1, 2, 8, 11-14]. 

Abstract Target-specific chiral selectors, which are characterized by a predictable elution order depending on the target enantiomer empioyed for the selection of the chirai selector, have recently received much attention in the enantioselective analysis fieid. In this context, bioaffinity-based molecular recognition toois such as nucleic acid aptamers have notabiy demonstrated very attractive features for the chiral discrimination of active moiecuies. In this chapter, the enantioseiective properties of aptamer chiral selectors and the major factors that control and modulate the liquid chromatography and capillary electrophoresis enantiomer separation are addressed. 

In this chapter, we focus particularly on the enantioselective properties of aptamers and their recent use as target-specific CSs in LC and CE. The main features of the aptamer-based chiral separations and the influence of two essential factors, i.e., the separation medium composition and the column/capillary temperature, on the enantiodiscrimination were especially emphasized. 

Aptamers have been successfully exploited in target-specific chiral separations both in LC (immobilized CS as chiral stationary phases, CSPs) and CE (CS added to the background electrolyte) [21-28]. Table 2 summarizes the different aptamer-based chiral stationary phases and the CE-based assays reported at the present time and the related chromatographic and electrophoretic results. 

The examples from the preceding discussion catalog the development of the field, which has largely led to increasing sophistication in the implementation of dipolar cycloadditions in target-specific molecule synthesis. The development of diastereoselective substrate-controlled methods as a general synthesis of chiral building blocks by use of nitrile-oxide dipolar cycloaddition reactions has only recently been heralded by the work of Kanemasa and Carreira. 

The screening was performed in a way similar to that of Welch, except that it involved the use of a spectropolarimeter instead of chiral chromatography to determine the selectivity. Equal amounts of the target racemate 17 were added into each of the 16 wells containing beads and the ellipticity of the supernatant liquid in each well was measured after equilibrating for 24 h at the wavelength of the maximum adsorption (260 nm). Knowing the specific ellipticity of one enantiomerically pure... 

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