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Investigating the effects of peptoid substitutions in self‐assembly of Fmoc‐diphenylalanine derivatives
Author(s) -
Rajbhandary Annada,
Nilsson Bradley L.
Publication year - 2017
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22994
Subject(s) - peptoid , chemistry , peptidomimetic , side chain , dipeptide , hydrogen bond , amino acid , self assembly , peptide , combinatorial chemistry , protein secondary structure , stereochemistry , polymer , organic chemistry , molecule , biochemistry
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.