From TgO/GABA-AT, GABA, and T-263 Mutant to Conception of Toxoplasma

Toxoplasma gondii causes morbidity, mortality, and disseminates widely via cat sexual stages. Here, we find T. gondii ornithine aminotransferase (OAT) is conserved across phyla. We solve TgO/GABA-AT structures with bound inactivators at 1.55 Å and identify an inactivator selective for TgO/GABA-AT over human OAT and GABA-AT. However, abrogating TgO/GABA-AT genetically does not diminish replication, virulence, cyst-formation, or eliminate cat's oocyst shedding. Increased sporozoite/merozoite TgO/GABA-AT expression led to our study of a mutagenized clone with oocyst formation blocked, arresting after forming male and female gametes, with “Rosetta stone”-like mutations in genes expressed in merozoites. Mutations are similar to those in organisms from plants to mammals, causing defects in conception and zygote formation, affecting merozoite capacitation, pH/ionicity/sodium-GABA concentrations, drawing attention to cyclic AMP/PKA, and genes enhancing energy or substrate formation in TgO/GABA-AT-related-pathways. These candidates potentially influence merozoite's capacity to make gametes that fuse to become zygotes, thereby contaminating environments and causing disease

An Efficient Route To S-N-(9-Fluorenylmethoxycarbonyl)-4'-(1-Azi-2,2,2-Trifluoroethyl)phenylalanine

An extremely efficient synthesis of optically pure photoactivatable phenylalanine derivative 1 is described. The key step involves a highly diastereoselective alkylation of a chiral glycine equivalent

Preparation of Novel 3H-Trifluoromethyldiazirine-Based Photoactivatable Potassium Channel Antagonists.

The preparation of a series of photoactivatable precursors for use in photoaffinity labelling of potassium channels is described. 3H-Diazirine functionalities were incorporated into the previously described potassium channel antagonists 1-3. The ability to perform enantioselective reductions and Wittig reactions in the presence of 3H-diazirines was central to this work. (c) 2005 Elsevier Ltd. All rights reserved

The synthesis and reactivity of optically pure amino acids bearingside-chain thioamides

The synthesis and reactivity of fully protected thioamide analogues of asparagine: and glutamine are described. A key feature of the synthetic strategies employed was the ability to perform selective thiations on multiple carbonyl-containing substrates. Also described are the preparations of thioamide derivatives of phenylalanine. The utility of these amino acid derivatives for solid-phase peptide synthesis is discussed