Beta-peptide bundles with fluorous cores

J Am Chem Soc. 2010 Mar 24;132(11):3658-9. doi: 10.1021/ja910903c.


We reported recently that certain beta-peptides self-assemble spontaneously into cooperatively folded bundles whose kinetic and thermodynamic metrics mirror those of natural helix bundle proteins. The structures of four such beta-peptide bundles are known in atomic detail. These structures reveal a solvent-sequestered, hydrophobic core stabilized by a unique arrangement of leucine side chains and backbone methylene groups. Here we report that this hydrophobic core can be re-engineered to contain a fluorous subdomain while maintaining the characteristic beta-peptide bundle fold. Like alpha-helical bundles possessing fluorous cores, fluorous beta-peptide bundles are stabilized relative to hydrocarbon analogues and undergo cold denaturation. Beta-peptide bundles with fluorous cores represent the essential first step in the synthesis of orthogonal protein assemblies that can sequester selectively in an interstitial membrane environment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Circular Dichroism
  • Crystallography, X-Ray
  • Kinetics
  • Models, Molecular
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Thermodynamics


  • Peptides