A new paradigm for protein design and biological self-assembly

Very few molecules with biological origins contain the element fluorine. Nature's inability to incorporate fluorine into biomolecules is related to the low concentration of free fluoride in sea and surface water. However, judicious introduction of fluorine into proteins, nucleic acids, lipids and carbohydrates has allowed mechanistic scrutiny of enzyme catalysis, control of protein oligomerization in membranes, clustered display of ligands on surfaces of living cells, and in increasing the protease stability of protein and peptide therapeutics.

Cartoon drawing of glucagon-like peptide-1 (GLP-1) poised to interact with its cognate receptor (GLP-1R). Several fluorinated analogues of GLP-1 containing hexafluoroleucine (shown) were prepared and their interaction with GLP-1R and subsequent cAMP production quantified. Residues 9 and 29 are highlighted in space filling depiction in GLP-1 and are representative of the replacements.Figure optionsDownload as PowerPoint slide