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A series of nonpeptide somatostatin agonists which bind selectively and with high affinity to somatostatin receptor subtype 2 (sst2) have been synthesized. One of these compounds, L-054,522, binds to human sst2 with an apparent dissociation constant of 0.01 nM and at least 3,000-fold selectivity when evaluated against the other somatostatin receptors. L-054,522 is a full agonist based on its inhibition of forskolin-stimulated adenylate cyclase activity in Chinese hamster ovary-K1 cells stably expressing sst2. L-054,522 has a potent inhibitory effect on growth hormone release from rat primary pituitary cells and glucagon release from isolated mouse pancreatic islets. Intravenous infusion of L-054,522 to rats at 50 [[micro]gram]/kg per hr causes a rapid and sustained reduction in growth hormone to basal levels. The high potency and selectivity of L-054,522 for sst2 will make it a useful tool to further characterize the physiological functions of this receptor subtype.

Cloning and analysis of the ETGI and FKSI genes of Saccharomyces cerevisiae reveal that both genes are identical and encode a 215-kDA integral membrane protein that consists of 16 transmembrane helices. The FKS1 gene also codes for a subunit of the echinocandin-resistant glucan synthase enzyme. Gene disruption induces a slow-growth phenotype, a rise in the sensitivity to echinocandin and decrease in the 1,3-beta-D-glucan synthase functions. The disruption mutant displays residual activity, indicating the presence of a glucan synthase isozyme.

A mutant strain of Saccharomyces cerevisiae, highly sensitive to the growth inhibition by immunosuppressants FK506 and cyclosporin A, is isolated. Hypersensitivity of this mutant is due to mutation fks1 which inhibits the activity of calcineurin phosphatase. The mutant consequently depends on the Ca2+ signal pathway for its growth, and offers a useful mechanism for greater understanding of immune suppression in yeast.

Two genes of Erwinia herbicola were needed for the growth of Escherichia Coli on tyrosine as the only source of nitrogen. The tutA gene encoding tyrosine phenol lyase was cloned in E. coli. The enzyme was secreted at levels that were high in the E. coli. The secretions took place in the presence of isoprophyl-beta-D-thiogalactopyranoside or lactose which acted as an inducer. The synthesis of L-dihydroxyphenylalamine was accomplished with catechol, pyruvate and ammonia by induceed cells.

The interactions of the immunosuppressants FK506 and cyclosporin A with their respective cytosolic receptors, FKBP-12 and cyclophilin, and calcineurin in the inhibition of recovery from alpha-mating factor arrest in yeast are similar to those involved in the inhibition of T-cell activation. In the inhibition of recovery of yeast from alpha-factor arrest, the drug-receptor complexes inhibit the calcineurin. These and other parallels suggest new directions for investigation into the Ca2+/calcineurin-dependent signal transduction pathways in yeast and T cells.