In this revised renewal application the principal investigator states that one of his long range objectives is to develop biocatalytic methods into a standard procedure so that they may be routinely used as a source of chiral organic reagents. He notes that to achieve this objective, it is necessary to gain a better understanding of the stereoselective behavior of biocatalysts, the reaction conditions most suitable for biocatalysis, and the development of new strategies for improving the stereoselective properties of enzymes. A second objective is to integrate biocatalytic processes with conventional chemical methods to produce novel and more efficient routes of synthesis of complex molecules in their enantiomerically-pure forms. It is stated that in this investigation, chemoenzymatic procedures will be employed to synthesize: a) novel analogs of cyclic ADP-ribose (cADPR), a putative second messenger involved in the regulation of Ca(+2) homeostasis. The principal investigator reports that it is a cyclic metabolite of NAD(+) and is as potent as inositol 1,4,5-triphosphate in mobilizing Ca(+2) in mammalian cells; b) the therapeutically important beta-lactam antibiotics. A third objective is to develop improved preparative methods for the condensation of peptide segments using 5(4H)-oxazolones as acyl donors and enzymatic methods for the synthesis of glycopeptides. Finally, it is noted that an interrelated project entails the isolation and characterization of cADPR receptor(s) from mammalian cells.
| Sih, C J; Shieh, W R; Chen, C S et al. (1986) Biochemical asymmetric catalysis. Ann N Y Acad Sci 471:239-54 |
