Aspects of Chirality

The essential step during in-vitro selection is amplification of the rare species represented in the combinatorial oligonucleotide library that bind to the target molecule. Amplification of nucleic acids can be accomplished very easily by employing enzymes - DNA polymerases (Box 16) - in a process called PCR. On the other hand, the degradation of aptamers occurs as a result of abundant nucleases which attack specific sites within the naturally configured nucleic acids. 

The basic concepts of stereochemistry were independently developed by varft Hoff and Le Bel in 1874. Based on their findings Emil Fischer suggested that biological macromolecules are composed of chiral l amino acids and d sugars and in 1894 proposed his famous key and lock hypothesis that two chiral molecules interact through shape complementarity with each other and are therefore stereospecific [15]. 

enantiomeric nucleic acids which are composed of mirror image nucleo- 

Unfortunately, enantiomeric or mirror-image nudeic adds cannot be used directly in the SELEX process because of the lack of (mirror-image) enzymes which would be needed to amplify them. 

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Method development remains the most challenging aspect of chiral chromatographic analysis, and the need for rapid method development is particularly acute in the pharmaceutical industry. To complicate matters, even structurally similar compounds may not be resolved under the same chromatographic conditions, or even on the same CSP. Rapid column equilibration in SFC speeds the column screening process, and automated systems accommodating multiple CSPs and modifiers now permit unattended method optimization in SFC [36]. Because more compounds are likely to be resolved with a single set of parameters in SFC than in LC, the analyst stands a greater chance of success on the first try in SFC [37]. The increased resolution obtained in SFC may also reduce the number of columns that must be evaluated to achieve the desired separation. 

SAC Wren, RC Rowe. Theoretical aspects of chiral separation in capillary electrophoresis. I. Initial evaluation of a model. J Chromatogr 603 235-241,... 

SAC Wren, RC Rowe. Theoretical aspects of chiral separation in capillary... 

A Rizzi. Fundamental aspects of chiral separations by capillary electrophoresis. Electrophoresis 22 3079-3106, 2001. 

Due to the importance of chiral drugs and pharmaceuticals, Witte et al. [7] and Rauws and Gioen [8] reviewed the status of regulatory aspects of chiral medicinal products in the pharmaceutical industries of the United States, Japan, and some European countries. The U.S. Food and Drug Administration (FDA) and other... 

This book discusses various aspects of chiral tine chemicals including their synthesis and uses at scale. There is an increasing awareness of the importance of chirality in biological molecules because the two enantiomers can sometimes have different effects.1" ... 

The third type of review primarily focused on the different aspects of chirality and contained some porphyrin-based supramolecular chirogenic systems as examples. For example, Finn, Wenzel, and Wilcox discussed various methods and reagents for the determination of ee and absolute configuration using different spectroscopic approaches [35,36] whilst Allenmark, Pasternack, Kobayashi, Formaggio et al. addressed the induced and electronic CD upon the intra- and intermolecular interactions considering several porphyrinoid chromophores [37-40]. 

T. O Brien, L. Crocker, R.Thompson, K. Thompson, P. Toma, D. Conlon, B. Feibush, C. Moeder, G. Bicker, and N. Grinberg, Mechanistic aspects of chiral discrimination on modified cellulose. Anal. Chem. 69 (1997), 1999-2007. 

Y. Bereznitski, R. Lobrutto, N. Variancaval, R. Thompson, K. Thopmpson, R Sajonz, L. S. Crocker, J. Kowal, D. Cai, M. Journet, T. Wang, J. Wyvratt, and N. Grinberg, Mechanistic aspects of chiral discrimination on an Amylose tris(3,5-dimethylphenyl)carbamate. Enantiomer 1 (2002), 305. 

Computational methods are increasingly being brought to bear on the crystallographic aspects of chiral crystals. The possibility that one could predict the crystal structures of a particular diastereomeric salt pair with an error in calculated lattice energy of less than 4 kcal/mole has been demonstrated for the system formed by a chlorine-substituted cyclic phosphoric acid and ephedrine [64]. In another study, it was demonstrated that the stability difference of the diastereomeric salt pairs of... 

S. A. C. Wren and R. C. Rowe, Theoretical aspects of chiral separation in capillary electrophoresis. 3. Application to beta-blockers,/. Chromatogr. 655 113 (1993). S. M., Branch, U., Holzgrabe, T. M., Jefferies, H. Mall-... 

Kutulya, L.A., Kuz min, V.E., Stel makh, I.B., Handrimailova, T.V. and Shtifanyuk, P.P. (1992). Quantitative Aspects of Chirality. III. Description of the Influence of the Structure of Chiral Compounds on Their Twisting Power in the Nematic Mesophase by Means of the Dissymmetry Function. J.Phys.Org.Chem., 5,308-316. 

Aspects of Chirality in Natural Products Drug Discovery... 

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