| Popis: |
Novel synthetic strategies based on the chemical models designed to simulate the enzyme action in some important biological processes have been developed. Successful chemical simulation of some vital cyclic operations of Nature, for example, ATP-Imidazole cycle - wherein a daughter imidazole is grown on a parent imidazole template via a cyclic pathway that is linked to the biosynthesis of the purine code bases ATP and GTP as well as to the imidazole amino acid histidine - and urea cycle wherein ornithine, a non-coded amino acid is used as a carrier molecule for urea via cyclic pathway that is linked to the biosynthesis of arginine - has provided a novel concept of the use of templates and carrier molecules in organic synthesis. A practical methodology for the synthesis of C-terminal amides from serine and threonine extended polypeptide precursors has been designed, patterned on the mechanism of action of pituitary enzymes for the generation of bioactive C-terminal polypeptide hormones from their glycine extended precursors. An aspect of enzyme action that has hitherto received scant attention is that in a large number of cases the reaction so mediated brings about changes remarkably close to those carried out with model systems under the laboratory conditions. Our endeavours at the chemical simulation of highly evolved and vital biological processes envisaged, inter alia, a correlation of processes 'mediated by enzymes on the one hand and those by using purely chemical means on the other. The long range objective of such study is to bring about a symbiosis of both enzymes and chemically mediated reactions to make the synthesis of complex target molecules effective. The work reported here would show that it is possible to bring about enzyme mediated changes effectively by chemical methodologies. The importance of this lies in the fact that chemically mediated processes are flexible in terms of substrates, reaction conditions and isolation procedures. We have also successfully demonstrated that the proper delineation of chemical means to bring about the enzyme mediated processes can be taken advantage of to generate novel strategies in organic synthesis for the preparation of substrates of biological importance. From this vantage, we have examined three carefully chosen key biological transformations, namely, the chemical simulation of the ATP-Imidazole cycle, the Urea cycle and a-amidating action of pituitary enzymes. |
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