Beta-peptide bundles with fluorous cores.
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.
Molski
Matthew A
MA
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.
Goodman
Jessica L
JL
Craig
Cody J
CJ
Meng
He
H
Kumar
Krishna
K
Schepartz
Alanna
A
D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
D010455:Peptides