Fluorocarbons have long been known for their chemical inertness, and their unique properties have found industrial and medical uses as fire retardants, refrigerants, anesthetics and biologically inert polymers. Recently, there has been much interest in whether fluorocarbon polymers can be exploited in the design of biological macromolecules, given their strong self-association and an affinity for lipid bilayers. Extensively fluorinated analogs of hydrophobic amino acids, when substituted into proteins and peptides, pack into the hydrophobic core of the protein, combining physicochemical properties with biological activity. For example, peptides designed like the “leucine zipper” domain of the transcription factor GCN4 display increased stability, enhanced self association and stronger receptor-ligand binding than their non-fluorinated counterparts. Hexafluoroleucine is a highly fluorinated analog of leucine, an amino acid that plays an important role in the folding of many proteins, yet until this point, the high materials cost, complicated synthesis method, and low purity yield have been prohibitive.
Researchers at the University of Michigan have invented a comparatively short and efficient method for preparing 5,5,5,5',5',5'-hexafluoroleucine and its protected analogs from commercially available and inexpensive starting materials. The claimed method can be used to prepare both L- and D-hFLeu enantiomers by utilizing starting materials having opposite stereochemistry.
Applications and Advantages
- Preparation of fluorous peptides and proteins
- Simpler synthesis method
- Lower materials cost
- Higher product yield