title: Investigating the effects of peptoid substitutions in self-assembly of Fmoc-diphenylalanine derivatives.
abstract: Low molecular weight agents that undergo self-assembly into fibril networks with hydrogel properties are promising biomaterials. Most low molecular weight hydrogelators are discovered empirically or serendipitously due to imperfect understanding of the mechanisms of self-assembly, the packing structure of self-assembled materials, and how the self-assembly process corresponds to emergent hydrogelation. Herein, the mechanisms of self-assembly and hydrogelation of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-PhePhe), a well-studied low molecular weight hydrogelator, is probed by systematic comparison with derivatives in which Phe residues are replaced by corresponding N-benzyl glycine peptoid (Nphe) analogs. Peptoids are peptidomimetics that shift display of side chain functionality from the α-carbon to the terminal nitrogen. This alters the hydrogen bonding capacity, the side chain presentation geometry, amide cis/trans isomerization equilibrium, and β-sheet potential of the peptoid relative to the corresponding amino acid in the context of peptidic polymers. It was found that amino acid/peptoid hybrids Fmoc-Phe-Nphe and Fmoc-Nphe-Phe have altered fibril self-assembly propensity and reduced hydrogelation capacity relative to the parent dipeptide, and that fibril self-assembly of the dipeptoid, Fmoc-Nphe-Nphe, is completely curtailed. These findings provide insight into the potential of low molecular weight peptoids and peptide/peptoid hybrids as hydrogelation agents and illuminate the importance of hydrogen bonding and π-π interaction geometry in facilitating self-assembly of Fmoc-Phe-Phe.
authors.affiliation: Department of Chemistry, University of Rochester, Rochester, New York.
authors.forename: Annada
authors.initials: A
authors.lastname: Rajbhandary
authors.affiliation: Department of Chemistry, University of Rochester, Rochester, New York.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Nilsson
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004151:Dipeptides; D005449:Fluorenes / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D057786:Peptidomimetics / Q000737:chemistry; D034444:Peptoids / Q000737:chemistry*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: C496789:9-fluorenylmethoxycarbonyl; D000596:Amino Acids; D001672:Biocompatible Materials; D004151:Dipeptides; D005449:Fluorenes; D010455:Peptides; D057786:Peptidomimetics; D034444:Peptoids; D012997:Solvents; C026650:phenylalanylphenylalanine; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D010649:Phenylalanine
keywords: hydrogel; peptide; peptoid; self-assembly