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1. Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials

   https://doi.org/10.1038/s41467-020-20689-w.  

   Wang F, Gnewou O (January 2021, Nature communications)

   null (Ed.)

   The exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture. Near-atomic resolution cryo-EM structural analysis of seven designed nanotubes provides insight into the designability of interfaces within these synthetic peptide assemblies and identifies a non-native structural interaction based on a pair of arginine residues. This arginine clasp motif can robustly mediate cohesive interactions between protofilaments within the cross-α nanotubes. The structure of the resultant assemblies can be controlled through the sequence and length of the peptide subunits, which generates synthetic peptide filaments of similar dimensions to flagella and pili. 

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2. Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials

   https://doi.org/10.1038/s41467-020-20689-w  

   Wang, Fengbin; Gnewou, Ordy; Modlin, Charles; Beltran, Leticia C.; Xu, Chunfu; Su, Zhangli; Juneja, Puneet; Grigoryan, Gevorg; Egelman, Edward H.; Conticello, Vincent P. (January 2021, Nature Communications)

   Abstract The exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture. Near-atomic resolution cryo-EM structural analysis of seven designed nanotubes provides insight into the designability of interfaces within these synthetic peptide assemblies and identifies a non-native structural interaction based on a pair of arginine residues. This arginine clasp motif can robustly mediate cohesive interactions between protofilaments within the cross-α nanotubes. The structure of the resultant assemblies can be controlled through the sequence and length of the peptide subunits, which generates synthetic peptide filaments of similar dimensions to flagella and pili. 

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3. Dueling Backbones: Comparing Peptoid and Peptide Analogues of a Mussel Adhesive Protein

   https://doi.org/10.1021/acs.macromol.9b02715  

   Wonderly, William R.; Cristiani, Thomas R.; Cunha, Keila C.; Degen, George D.; Shea, Joan-Emma; Waite, J. Herbert (August 2020, Macromolecules)

   Ensembles of amino acid side chains often dominate the interfacial interactions of intrinsically disordered proteins; however, backbone contributions are far from negligible. Using a combination of nanoscale force measurements and molecular dynamics simulations, we demonstrated with analogous mussel-mimetic adhesive peptides and peptoids both 34 residues long that highly divergent adhesive/cohesive outcomes can be achieved on mica surfaces by altering backbone chemistry only. The Phe, Tyr, and Dopa containing peptoid variants used in this study deposited as dehydrated and incompressible films that facilitated analysis of peptoid side chain contributions to adhesion and cohesion. For example, whereas Phe and Dopa peptoids exhibited similar cohesion, Dopa peptoids were ∼3 times more adhesive than Phe peptoids on mica. Compared with the peptides, Phe peptoid achieved only ∼20% of Phe containing peptide adhesion, but the Dopa peptoids were >2-fold more adhesive than the Dopa peptides. Cation−π interactions accounted for some but not all of the cohesive interactions. Our results were corroborated by molecular dynamics simulations and highlight the importance of backbone chemistry and the potential of peptoids or peptoid/peptide hybrids as wet adhesives and primers. 

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4. Factors Affecting Secondary and Supramolecular Structures of Self‐Assembling Peptide Nanocarriers

   https://doi.org/10.1002/mabi.202100347  

   Pitz, Megan E.; Nukovic, Alexandra M.; Elpers, Margaret A.; Alexander‐Bryant, Angela A. (November 2021, Macromolecular Bioscience)

   Abstract Self‐assembling peptides are a popular vector for therapeutic cargo delivery due to their versatility, tunability, and biocompatibility. Accurately predicting secondary and supramolecular structures of self‐assembling peptides is essential for de novo peptide design. However, computational modeling of such assemblies is not yet able to accurately predict structure formation for many peptide sequences. This review identifies patterns in literature between secondary and supramolecular structures, primary sequences, and applications to provide a guide for informed peptide design. An overview of peptide structures, their applications as nanocarriers, and analytical methods for characterizing secondary and supramolecular structure is examined. A top‐down approach is then used to identify trends between peptide sequence and assembly structure from the current literature, including an analysis of the drivers at work, such as local and nonlocal sequence effects and solution conditions. 

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5. Multivalent display of chemical signals on self‐assembled peptide scaffolds

   https://doi.org/10.1002/pep2.24224  

   Distaffen, Hannah E.; Jones, Christopher W.; Abraham, Brittany L.; Nilsson, Bradley L. (March 2021, Peptide Science)

   Abstract Self‐assembled peptide materials have emerged as promising bioinspired tools for applications that include regenerative medicine, drug delivery, antimicrobial and vaccine development, optics, and catalysis. Peptide self‐assembly mediated by noncovalent hydrogen bonding, coulombic, hydrophobic, and aromatic interactions gives rise to a variety of supramolecular structures that reflect on the nature of the constituent peptides. The emergent properties of these supramolecular peptide materials often depend on the multivalent presentation of functional appendages on the self‐assembled scaffold. For example, the multivalent display of cell‐signaling motifs on self‐assembled peptide nanofibrils provides materials that are excellent extracellular matrix mimetics for tissue engineering applications. This review includes a discussion of chemical strategies that address the challenge of appending functional signal motifs in a multivalent display on self‐assembled peptide and protein materials. In addition, recent examples of supramolecular peptide materials that rely on the multivalent display of chemical signals for the desired applications are presented. Collectively, this discussion illustrates the potential of self‐assembled peptides as sustainable materials to address challenges in contemporary materials science and provides principles for the design of next‐generation agents for a variety of applications. 

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