Biosynthesis and Stability of Coiled‐Coil Peptides Containing (2S,4R)‐5,5,5‐Trifluoroleucine and (2S,4S)‐5,5,5‐Trifluoroleucine

Life in stereo: We report the effects of 5,5,5-trifluoroleucine (TFL) stereochemistry on coiled-coil peptide biosynthesis and stability. We demonstrate that two diastereoisomers of TFL are activated and incorporated into peptides expressed in E. coli. Coiled-coil homodimers of these peptides exhibited increased stability. An equimolar mixture of the two fluorinated peptides formed a heterodimer of modestly enhanced thermal stability relative to the homodimers (see figure).