Steroids imprinting

Fig. 16. Screening of a steroid library using (top) MIP prepared against 11-a-hydroxyproges-terone (1), gradient elution using (bottom) non-imprinted control polymer, isocratic elution. Reprinted with permission from Ramstrom O, Ye L, Krook M, Mosbach K (1998) Anal Com-mun 35 9. Copyright 1998 The Royal Society of Chemistry...

Comparable results were presented when the number of Mi-polymers was extended to other templates of similar steroid libraries. The use of a polymer imprinted with 11-deoxycortisol in a separation of 11-a-hydroxyprogesterone, progesterone and 11-deoxycortisol resulted in a chromatogram where the 11-de-oxycortisol eluted last (Fig. 17, bottom). When an 11-a-hydroxyprogesterone imprinted polymer was used, on the other hand, the 11 -a-hydroxyprogesterone was found to elute last (Fig. 17, top) [80]. 

Skett P, Gustafsson J-A. Imprinting of enzyme systems of xenobiotic and steroid metabolism. Rev Biochem Tox 1979 1 27. 

A few years later, in 1993, Akermark et al. reported the preparation of imprinted polymers capable of reducing selectively a 3-17-steroidal diketone (21) to the corresponding alcohol with high control of the stereochemistry [13]. The polymers were prepared attaching a polymerisable unit via an ester linkage to the desired steroidal product in position 17 (Fig. 3). The resulting compound was then used as a... 

The boronic acid binding site can also be used for interactions with monoalcohols. In the presence of an ort/zo-hydroxymethylene group (see entry 1), an intramolecular cyclic monoester is formed (boronophthalide). This compound still has one hydroxyl group left for the esterification of monoalcohols, a reaction that can be used in the imprinting procedure [46,47,72]. Recently this method has been revived for the binding of steroid alcohols [73,986,c]. 

In most studies, the selectivities of the MIPs have been estimated by measuring the amount of each ligand required to displace 50% of the binding of radiolabelled imprint species to the MIP (IC50). The first MIA study reported excellent selectivity of the theophylline method for theophylline (1,3-dimethylxanthine) in the presence of the structurally related compound caffeine (1,3,7-trimethylxanthine) [3]. Despite their close resemblance (they differ by only one methyl group), caffeine showed less than 1 % cross-reactivity. A similar level of specificity was recorded for cortisol and corticosterone MIPs, which were able to detect the absence and presence of single hydroxyl groups and double bonds in the steroid structure [13]. 

Molecular imprinting [1] is now an established technique for the creation of polymeric matrices with predetermined affinity for particular substrates. The technique has been used for the creation of substrates with affinities for amino acids, peptides, proteins, nucleotides and nucleosides, carbohydrates, various drugs (e.g. opiates, alkaloids, antibiotics, /1-blockers, tranquillisers) and other bioactive compounds (e.g. enkephalin, steroids, corticosteroids), herbicides, pesticides, as well as metal ions and a number of miscellaneous organic compounds [2-5]. 

Ramstrom, O., Ye, L., Krook, M., Mosbach, K. Screening of a combinatorial steroid library using molecularly imprinted polymers Anal. Comm., 1998, 35, 9-11... 

The non-covalent molecular imprinting approach has been applied to a broad range of templates, including free amino acids [24], protected amino acids [25-31], herbicides [32-37], pesticides [38], fungicides [39], narcotics [40], antibiotics [41— 47], barbiturates [48] and steroids [49-52]. The non-covalent approach is not restricted to small molecules but has also been applied to the imprinting of larger molecules such as proteins [53-55] and even bacteria [56],... 

The development of an imprinted network starts with the choice of the template molecule. It is this molecule that the material will keep in memory. The choice remains limited, however, by the functional monomers available and susceptible to interact. Depending on the domain studied, diverse molecules have been used (Fig. 5) amino acids [26],sugar derivatives [27], steroids [28], nucleotides [29], pesticides [30], dyes [12], drugs [31-36], metal ions [37-39], more inert molecules (like anthracene, benzene and its derivatives) [40-42], and even more complex molecules such as proteins or enzymes [43,44]. 

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