Chemical-enzymic synthesis

Preparation of modified, bacterial polysaccharides having monosaccharide analogs inserted into the polymeric chain is of interest for study of the structure-properties relationship in these biopolymers. Incorporation of chemically prepared, modified, biosynthetic precursors of the polymers in enzymic reactions seems a promising approach for achieving this aim. Such an approach, which may be termed chemical-enzymic synthesis, has now been studied by our group,439-441 using O-specific polysaccharides (10-12) of Salmonella serogroups B and E as an example. 

Yuasa H, Hindsgaul O, Palcic MM (2002) Chemical-enzymic synthesis of 5 -thio-N-acetyllactosamine the first disaccharide with sulfur in the ring of the non-reducing sugar. J Am Chem Soc 114 5891-5892... 

Schuster M, Wang P, Paulson JC, Chi-Huey WongSchuster. Solid-phase chemical-enzymic synthesis of glycopeptides and oligosaccharides, J. Am. Chem. 

Ichikawa Y, Lin YC, Dumas DP, Shen GJ, Garcia-Junceda E, Williams MA, Bayer R, Ketcham C, Walker EE, Paulson JC, Wong CH. Chemical-enzymic synthesis and conformational analysis of sialyl Lewis X and derivatives. J Am Chem Soc 1992 114 9283-9298. 

Mel 1994 Meldal, M., Auzanneau, F.-L, Hindsgaul, O. and Palcic, M.M., A PEGA Resin for Use in the Solid-Phase Chemical-Enzymic Synthesis of Glycopeptides, J. Chem. Soc., Chem. Commun., (1994) 1849-1850. 

Enzymic and Chemical Synthesis of the a-l 2-glucosidic Linkage Enzymic Synthesis, S. A. Barker, E. J. Bourne, P. M. Grant, andM. Stacey, Nature, 178(1956) 1221-1223. 

D-Glucose 6-phosphate is converted enzymically into L-wyo-inositol 1-phosphate (20) in a process which requires NAD+. The base-catalysed cyclization of d-xylo-hexos-5-ulose 6-phosphate (21), followed by reduction with borohydride, leads to (20) and epi-inositol 3-phosphate (22) (Scheme 3).59 This has been put forward as a chemical model for the enzymic synthesis. The phosphorylation of inositols with polyphosphoric acid has been described80 and the p-KVs of inositol hexaphosphate have been determined by 31P n.m.r.61... 

This unnatural acid is used as a chiral intermediate for the synthesis of a number of products. Chemical asymmetric synthesis was very difficult and so the stereoselective synthetic properties of enzymes were exploited to carry out a selective reduction reaction. The stereoselective hydrolysis of protein amino acid esters had already been commercialised by Tanabe in Japan using immobilised aminoacylase, and selective reduction reactions using whole yeast cells are already used in a number of processes, such as the selective reduction of the anti-cancer drag Coriolin. 

Usually a biocatalyst-based process is in competition with other approaches, for instance enzyme resolution processes to produce single isomer products are in competition with their isolation from natural sources and chemical asymmetric synthesis processes. 

The chemical-enzymic approach to the synthesis of modified polysaccharides presents a good prospect for the preparation of small quantities of these polymers, which may prove very useful for immunochemical studies. The approach is certainly not limited by the specific case of Salmonella polysaccharides 10-12, and may well be extended to other polymers. The first results from this group322 show that several analogs of O-specific polysaccharides (18) of Salmonella serogroups C2 and C3 may be prepared through this approach. 

U. Kragl, M. Kittelmann, O. Ghisalba, and C. Wandrey, N-Acetylneuraminic add from a rare chemical from natural sources to a multikilogram enzymic synthesis for industrial application, Ann. N. Y. Acad. Sci. USA 1995, 750, 300-305. 

Mode of isolation A. chemical synthesis B. enzymic synthesis C. degradation of oligosaccharide D. degradation of polysaccharide E. naturally occurring. 

Induction by increased enzyme synthesis has been described for induction of CYP2B1/2 by octamethylcyclotetrasiloxane (Sarangapani et al. 2002) and CYP1A1 and CYP1A2 by TCDD via interaction with the Ah-receptor (Andersen 1995 Andersen et al. 1997). Induction by decreased enzyme degradation has been described by Chien et al. (1997) for induction of CYP2E1 by ethanol, acetone, and isoniazid via enzyme stabilization. Exposure to such enzyme inducers and stabilizators would result in increasing the clearance of all other coexposed chemicals that are metabolized by the stabilized enzyme. 

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