The (S) -Nme t h y I -y-[ 4-(t r if 1 u o r o m e t h y I ) p h e n ox y ] be n ze n e p ro p a n a m i n e , an antidepressant with potential applications in the treatment of other illnesses was labelled with fluorine-1 8 for Positron Emission Tomography studies. The synthesis was accomplished from the [18F]-4-~hlorobenzotrifluoride where [18F]-label was introduced via a nucleophilic aliphatic substitution reaction.[18F]-(S)-Fluoxetine was obtained with a radiochemical yield of 9-1 0% (decay corrected) and a specific radioactivity of 100-150 mCi/kmol (3.70-5.55 GBq/pmol) in a total synthesis time of 150 min. A facile isotopic exchange reaction was desmonstrated; it is expected to reduce the specific activity of the final [18F]-product. The experimental parameters play an important role, which is discussed.

L-Tryptophan 2,3-oxidase, an amino acid ␣,␤-dehydrogenase isolated from Chromobacterium violaceum, catalyzes the formation of a double bond between the C ␣ and C ␤ carbons of various tryptophan derivatives provided that they possess: (i) a L-enantiomeric configuration, (ii) an ␣-carbonyl group, and (iii) an unsubstituted and unmodified indole nucleus. Kinetic parameters were evaluated for a series of tryptophan analogues, providing information on the contribution of each chemical group to substrate binding. The stereochemistry of the dehydro product was determined to be a Zconfiguration from proton nuclear magnetic resonance assignments. No reaction can be observed in the presence of other aromatic ␤-substituted alanyl residues which behave neither as substrates nor as inhibitors and therefore do not compete against this reaction. The enzymatic synthesis of ␣,␤-dehydrotryptophanyl peptides from 5 to 24 residues was successfully achieved without side product formation, irrespective of the position of the tryptophan residue in the amino acid sequence. A reactional mechanism involving a direct ␣,␤-dehydrogenation of the tryptophan side chain is proposed.

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Upon agonist activation, the nicotinic acetylcholine receptor undergoes allosteric transitions leading to channel opening and sodium ion influx. The molecular structure of the agonist binding site has been mapped previously by photoaffinity labeling, but most photosensitive probes used for this purpose interact only with closed receptor states (resting or desensitized). We have synthesized two novel photoactivatable 4-diazocyclohexa-2,5-dienone derivatives as cholinergic agonist candidates, with the objective of identifying structural changes at the acetylcholine binding site associated with receptor activation. One of these ligands, 9b, is a functional agonist at muscle acetylcholine receptors in human TE 671 cells. In photolabeling experiments with 9b, up to 35% inactivation of agonist binding sites was observed at Torpedo acetylcholine receptors. Tritiated 9b was synthesized, and photolabeling was found to occur mainly on the alpha-subunit in a partially protectable manner. This novel radiolabeled photoprobe appears to be suitable for future investigation of the molecular dynamics of allosteric transitions occurring at the active acetylcholine receptor binding site.