title: Lyotropic liquid crystals formed from ACHC-rich β-peptides.
abstract: We have examined the effect of β-peptide modifications on the propensity of these helical molecules to form lyotropic liquid crystalline (LC) phases in water. All of the β-peptides we have examined contain 10 residues. In each case, at least three residues are derived from trans-2-aminocyclohexanecarboxylic acid (ACHC), which strongly promotes folding to a 14-helical conformation. The structural features varied include the number of ACHC residues, the nature and spatial arrangement of charged side chains (cationic vs anionic), and the identity of groups at the β-peptide termini. We found that relatively small changes (e.g., swapping the positions of a cationic and an anionic side chain) could have large effects, such as abrogation of LC phase formation. The trends revealed by sequence-property studies led to the design of LC-forming β-peptides that bear biomolecular recognition groups (biotin or the tripeptide Arg-Gly-Asp). Structural analysis via circular dichroism and cryo-transmission electron microscopy revealed the existence of two different types of self-associated species, globular aggregates and nanofibers. Nanofibers are the predominant assembly formed at concentrations that lead to LC phase formation, and we conclude that these nanofibers are the functional mesogens. Overall, these studies show how the modularity of β-peptide oligomers enables elucidation of the relationship between molecular structure and large-scale self-assembly behavior.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
authors.forename: William C
authors.initials: WC
authors.lastname: Pomerantz
authors.forename: Virany M
authors.initials: VM
authors.lastname: Yuwono
authors.forename: Ryan
authors.initials: R
authors.lastname: Drake
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Hartgerink
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Abbott
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry*; D003514:Cyclohexylamines / Q000737:chemistry*; D050866:Liquid Crystals / Q000737:chemistry*; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D003509:Cyclohexanecarboxylic Acids; D003514:Cyclohexylamines; D009842:Oligopeptides; D010455:Peptides; C103271:2-aminocyclohexanecarboxylic acid; C047981:arginyl-glycyl-aspartic acid