Synthesis and Selection of Pla2 Inhibitors

We will use a combinatorial unrandomization technique to identify inhibitors of two human phospholi(PLA/2) enzymes, type II and cytosolic. PLA/2-catalyzed hydrolysis of membrane phospholipids is thethe production of a number of proinflammatory eicosanoids and production of the enzyme is regulatedcytokines. Thus, PLA/2 occupies a central position in the inflammatory cascade. The aims of this prolibraries of random oligomers from phosphoramidite monomers derivatized with diverse functional groulibraries for inhibition of PLA/2 enzymatic activity. A unique compound will be identified using anscreening approach. This combinatorial unrandomization technique that has been used to select a phosof HIV envelope-mediated cell fusion (Wyatt et al. Proc. Natl. Acad. Sci., 1994).