Amino acids, fluorinated methionine

Many bacterial enzymes and proteins, which are modified by the introduction of F-Phe or F-Tryp, have been obtained. Mammalian proteins containing F-Pro or other fluorinated amino acids have also been obtained, either in a direct manner in vivo) or, more efficiently, by the expression of the gene in a bacteria. Thus, trifluoro-methionine has been incorporated by E. coli in the lysozyme of a bacteriophage. Because this enzyme contains three methionines, it has been used to study the interactions of this protein with its ligands by F NMR. ... 

This chapter focuses on how fluorinated methionine analogues interact with biological systems. Specifically the compounds L-monofluoromethionine (l-(S)-(monofluoromethyl) homocysteine MFM), L-difluoromethionine (L-(S)-(difluoromethyl)homocysteine DFM), and L-trifluoromethionine (L-(S )-(trifluoromethyl(homocysteine) TFM) will be the subject of this article (Figure 17.1). A discussion of their syntheses and chemical and conformational properties will be presented. This will be followed by a discussion of their incorporation into peptides and proteins and the properties of the resulting fluorinated biomolecules. The 19F NMR spectroscopic characteristics of these biomolecules will be covered along with how these resonances have revealed information on the properties of the difluoro- and trifluoromethyl moiety (and on the proteins as well ). Further elaboration of these amino acids with metalloenzymes completes the survey. 

Although DFM and TFM are important contributions to the range of spectroscopic probes available for application to biochemical studies, other properties of these fluorinated amino acid analogues can also be of use. For example, the subtle change in size of the thiomethyl group and the alteration in the electronic properties of the sulfur atom in these methionine analogues could be useful properties to explore biological systems. In order to obtain... 

The panel of fluorinated amino acids incorporated into peptides and proteins has seen tremendous growth in the past decade. Analogs of valine, leucine, isoleucine, methionine, alanine, and phenylalanine have been synthesized with varying numbers of fluorine atoms and incorporated into naturally occurring and de novo designed proteins and peptides. As leucine is the most widely found amino acid in proteins, trifluoroleucine and hexafluoroleucine deserve special mention as widely studied residues in peptide and protein design. 

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