The production of enkephalins, like the biosynthesis of other hormones, involves a sequential series of enzymatic steps culminating in the liberation of the active opioid sequences. Opioid peptides have been implicated in physiological processes ranging from blood pressure control to immunological function; the biochemical basis for the addictive properties of drugs may also relate to deficiencies in endogeneous levels or in the turnover of opioid peptides. It is therefore important to gain a good understanding of the biochemical mechanisms involved in opioid peptide biosynthesis. My short-term goals are to define the sequence of cleavages of proenkephalin as well as to investigate the presence of posttranslational modifications. Other short-term goals relate to the study of a putative proenkephalin processing enzyme, a serine protease present in chromaffin granules. My long- term objectives are to understand how biologically active peptides are synthesized. Ultimately I would like to be able to study the cellular regulation of proenkephalin processing, and to use molecular biological techniques to investigate general questions relating to the specificity of hormone processing proteases. The RCDA, if awarded, will assist me in accomplishing the goals outlined above in two ways. Firstly, it will free me from Departmental obligations such as substantial teaching in service courses, enabling me to devote my complete attention to research throughout the year. Secondly, by securing this award, I will be exempted from service on additional committees, both at a Departmental and Institutional level. The Department of Biochemistry and Molecular Biology provides a supportive environment for the development of my research career. The newly-established peptide synthesis/sequencing facility will enable on-site synthesis of peptides required for the above studies. Resource personnel able to provide direction in the techniques of molecular cloning are also present. The fact that Department faculty receive considerable support from federal granting agencies means that expertise and equipment is readily available through active research programs in surrounding laboratories. In short, the environment at L.S.U. provides an extremely favorable milieu in which to carry out the studies described in this proposal. The award of an RCDA will greatly speed the rate at which these studies are accomplished.
| Vindrola, O; Lindberg, I (1992) Biosynthesis of the prohormone convertase mPC1 in AtT-20 cells. Mol Endocrinol 6:1088-94 |
| Lindberg, I (1991) The new eukaryotic precursor processing proteinases. Mol Endocrinol 5:1361-5 |
| Shen, F S; Roberts, S F; Lindberg, I (1989) A putative processing enzyme for proenkephalin in bovine adrenal chromaffin granule membranes. Purification and properties. J Biol Chem 264:15600-5 |
