Enzymes positron emission tomography

Numerous other amino acid decarboxylases have been isolated and characterized, and much interest has been shown as a result of the irreversible nature of the reaction with the release of C02 as the thermodynamic driving force. Although these enzymes have narrow substrate-specificity profiles, their utility has been widely demonstrated. Additional industrial processes will continue to be developed once other decarboxylases become available. Such biocatalysts would include the aromatic amino acid (E.C. 4.1.1.28), phenylalanine (E.C. 4.1.1.53) and tyrosine (E.C. 4.1.1.25) decarboxylases, which likely could be used to produce derivatives of their respective substrates. These derivatives are finding increased use in the development of peptidomimetic drugs and as possible positron emission tomography imaging agents.267-268... 

Comparison of the disposition of the two enantiomers of selegiline by the novel positron emission tomography methodshowed that both isomers were distributed very quickly. However, since the D-isomer hardly binds to MAO B, its clearance was much faster than that of the L-isomer. Interestingly, the clearance of the ( C) L-isomer was as fast as the d-isomer in a patient in whom MAO B was already inhibited by previous treatment with selegiline. This observation confirms that covalent binding to the enzyme is the major reason for the slower clearance of the active L-isomer than that of the D-isomer. 

Nuclear medicine - in particular, positron emission tomography (PET) - is one of the emerging, important fields of practical application of iodonium salts. PET is a powerful and rapidly developing area of molecular imaging that is used to study and visualize human physiology by the detection of positron-emitting radiopharmaceuticals [50-55], PET experiments provide direct information about metabolism, receptor/enzyme... 

No 3-azido, 3-amino, or Boc-protected mannosamine analogs 12 were accepted by the enzyme (Figure 5.11) [98] which suggests that the presence of a 3-hydroxyl group is a necessary precondition for substrates of the aldolase. Likewise, conformationally inflexible acrylate 13 was not accepted in cleavage direction. By use of fluoropyruvate 15 as the donor substrate a series of dia-stereomeric 3-deoxy-3-fluoro ulosonic acids such as 16 has been prepared in good yields (>49%) from pentoses or hexoses [82]. Such products are attractive for non-invasive in-vivo pharmacokinetic studies by NMR tomography ( F derivatives) or positron-emission spectroscopy ( F derivatives). 

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