Abstract
Peptoids are biofunctional N-substituted glycine peptidomimics. Their self-assembly is of fundamental interest because they demonstrate alternatives to conventional peptide structures based on backbone chirality and beta-sheet hydrogen bonding. The search for self-assembling, water-soluble “minimal” sequences, be they peptide or peptidomimic, is a further challenge. Such sequences are highly desired for their compatibility with biomacromolecules and convenient synthesis for broader application. We report the self-assembly of a set of trimeric, water-soluble α-peptoids that exhibit a relatively low critical aggregation concentration (CAC ∼ 0.3 wt %). Cryo-EM and angle-resolved DLS show different sequence-dependent morphologies, namely uniform ca. 6 nm wide nanofibers, sheets, and clusters of globular assemblies. Absorbance and fluorescence spectroscopies indicate unique phenyl environments for π-interactions in the highly ordered nanofibers. Assembly of our peptoids takes place when the sequences are fully ionized, representing a departure from superficially similar amyloid-type hydrogen-bonded peptide nanostructures and expanding the horizons of assembly for sequence-specific bio- and biomimetic macromolecules.
Highlights
Very short selfassembling peptides and their mimics (e.g., ≤ 5 residues) are of special interest since they are more scalable and they lead to insight into assembly requirements.[1]. Their discovery is nontrivial since assembly propensity and favorable solvent interactions must be balanced among just a few residues.[1−3] The realization that diphenylalanine (FF) is a key aggregating domain of amyloid peptides including amyloid β4−6 has had an immense impact since assembly from such a simple dipeptide was not anticipated
The side chain shift eliminates backbone hydrogen-bond (H-bond) donors, and intraand interbackbone H-bonding. This means that the peptoid backbone may be freely hydrated[20,21] and, together with lack of backbone chirality, may exhibit great conformational flexibility.[10,22]
Inspired by FF and derivatives, we prepared a set of four achiral peptoid trimers comprised of analogs of the aromatic amino acid phenylalanine and the cationic lysine
Summary
King Hang Aaron Lau − Department of Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, U.K.; orcid.org/0000-0003-3676-9228; Email: Aaron.Lau@ strath.ac.uk. Authors Jani Seitsonen − Nanomicroscopy Center, Aalto University, FIN-02150 Espoo, Finland Kunal M. Tewari − Department of Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, U.K. Abshar Hasan − Department of Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, U.K.; Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India Robert M. Edkins − Department of Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, U.K.; orcid.org/ 0000-0001-6117-5275 Janne Ruokolainen − Nanomicroscopy Center, Aalto University, FIN-02150 Espoo, Finland Lalit M. Pandey − Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
