title: Design, synthesis, and study of fluorinated proteins.
abstract: Highly fluorinated analogs of hydrophobic amino acids have proven to be generally effective in increasing the thermodynamic stability of proteins. These non-proteogenic amino acids can be incorporated into both α-helix and β-sheet structural motifs and generally enhance protein stability towards unfolding by heat and chemical denaturants, and retard their degradation by proteases. Recent detailed structural and thermodynamic studies have demonstrated that the increase in buried hydrophobic surface area that accompanies fluorination is primarily responsible for the stabilizing properties of fluorinated side chains. Fluorination appears to be a particularly useful strategy for increasing protein stability because fluorinated amino acids closely retain the shape of the side chain, and are thus minimally perturbing to protein structure and function. The first part of this chapter discusses some examples of highly fluorinated model proteins designed by our laboratory and protocols for their synthesis. In the second part, methods for determining their thermodynamic stability, along with conditions that have proven to be useful for crystallizing these proteins, are presented.
authors.affiliation: Department of Chemistry, University of Michigan, 930 N. University Ave., Ann Arbor, MI, 48109, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Buer
authors.forename: E Neil G
authors.initials: EN
authors.lastname: Marsh
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D054879:Halogenation / Q000502:physiology; D057927:Hydrophobic and Hydrophilic Interactions; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000138:chemical synthesis* / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins