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1. Using Self-Assembling Peptides to Integrate Biomolecules into Functional Supramolecular Biomaterials

   https://doi.org/10.3390/molecules24081450  

   Liu, Renjie; Hudalla, Gregory A. (April 2019, Molecules)

   Throughout nature, self-assembly gives rise to functional supramolecular biomaterials that can perform complex tasks with extraordinary efficiency and specificity. Inspired by these examples, self-assembly is increasingly used to fabricate synthetic supramolecular biomaterials for diverse applications in biomedicine and biotechnology. Peptides are particularly attractive as building blocks for these materials because they are based on naturally derived amino acids that are biocompatible and biodegradable; they can be synthesized using scalable and cost-effective methods, and their sequence can be tailored to encode formation of diverse architectures. To endow synthetic supramolecular biomaterials with functional capabilities, it is now commonplace to conjugate self-assembling building blocks to molecules having a desired functional property, such as selective recognition of a cell surface receptor or soluble protein, antigenicity, or enzymatic activity. This review surveys recent advances in using self-assembling peptides as handles to incorporate biologically active molecules into supramolecular biomaterials. Particular emphasis is placed on examples of functional nanofibers, nanovesicles, and other nano-scale structures that are fabricated by linking self-assembling peptides to proteins and carbohydrates. Collectively, this review highlights the enormous potential of these approaches to create supramolecular biomaterials with sophisticated functional capabilities that can be finely tuned to meet the needs of downstream applications. 

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2. Mechanomorphogenic Films Formed via Interfacial Assembly of Fluorinated Amino Acids

   https://doi.org/10.1002/adfm.202104223  

   Sloand, Janna N.; Culp, Tyler E.; Wonderling, Nichole M.; Gomez, Enrique D.; Medina, Scott H. (June 2021, Advanced Functional Materials)

   Abstract Nature has evolved several elegant strategies to organize inert building blocks into adaptive supramolecular structures. Favored among these is interfacial self‐assembly, where the unique environment of liquid–liquid junctions provides structural, kinetic, thermodynamic, and chemical properties that are distinct from the bulk solution. Here, antithetical fluorous–water interfaces are exploited to guide the assembly of non‐canonical fluorinated amino acids into crystalline mechanomorphogenic films. That is, the nanoscale order imparted by this strategy yields self‐healing materials that can alter their macro‐morphology depending on exogenous mechanical stimuli. Additionally, like natural biomolecules, organofluorine amino acid films respond to changes in environmental ionic strength, pH, and temperature to adopt varied secondary and tertiary states. Complementary biophysical and biochemical studies are used to develop a model of amino acid packing to rationalize this bioresponsive behavior. Finally, these films show selective permeability, capturing fluorous compounds while allowing the free diffusion of water. These unique capabilities are leveraged in an exemplary application of the technology to extract perfluoroalkyl substances from contaminated water samples rapidly. Continued exploration of these materials will advance the understanding of how interface‐templated and fluorine‐driven assembly phenomenon a can be co‐utilized to design adaptive molecular networks and living matter. 

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3. Visible-light photooxidation in water by ¹ O ₂ -generating supramolecular hydrogels

   https://doi.org/10.1039/C9SC06481H  

   Biswas, Sankarsan; Kumar, Mohit; Levine, Andrew M.; Jimenez, Ian; Ulijn, Rein V.; Braunschweig, Adam B. (April 2020, Chemical Science)

   null (Ed.)

   We report supramolecular photocatalytic hydrogels, produced by the enzymatically driven self-assembly of low molecular weight gelators (LMWGs). These LMWG precursors are composed of the organic chromophore diketopyrrolopyrrole (DPP), which is bi-functionalized with a series of amino acid (Phe, Tyr, Leu) methyl esters. In situ enzymatic hydrolysis of these photoactive precursors results in supramolecular hydrogels that provide a high density of photocatalytic sites. Under visible light irradiation these hydrophobic fibers recruit the reaction substrates and also produce 1 O 2 , which is used here for the photooxidation of thioanisole (aromatic substrate) and cyclohexyl methyl sulfide (aliphatic substrate), with yields as high as 100% and without over-oxidation. Finally, we demonstrate that the nature of the amino acids in the LWMGs has a central role in dictating J-/H-/mixed state aggregates, gel properties, and, hence, the efficiency of chemoselective photooxidation of thioanisole and cyclohexyl methyl sulfide inside these hydrogels. 

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4. Capacity for increased surface area in the hydrophobic core of β ‐sheet peptide bilayer nanoribbons

   https://doi.org/10.1002/psc.3334  

   Jones, Christopher W.; Morales, Crystal G.; Eltiste, Sharon L.; Yanchik‐Slade, Francine E.; Lee, Naomi R.; Nilsson, Bradley L. (June 2021, Journal of Peptide Science)

   Amphipathic peptides with amino acids arranged in alternating patterns of hydrophobic and hydrophilic residues efficiently self‐assemble intoβ‐sheet bilayer nanoribbons. Hydrophobic side chain functionality is effectively buried in the interior of the putative bilayer of these nanoribbons. This study investigates consequences on self‐assembly of increasing the surface area of aromatic side chain groups that reside in the hydrophobic core of nanoribbons derived from Ac‐(XKXE)₂‐NH₂peptides (X = hydrophobic residue). A series of Ac‐(XKXE)₂‐NH₂peptides incorporating aromatic amino acids of increasing molecular volume and steric profile (X = phenylalanine [Phe], homophenylalanine [Hph], tryptophan [Trp], 1‐naphthylalanine [1‐Nal], 2‐naphthylalanine [2‐Nal], or biphenylalanine [Bip]) were assessed to determine substitution effects on self‐assembly propensity and on morphology of the resulting nanoribbon structures. Additional studies were conducted to determine the effects of incorporating amino acids of differing steric profile in the hydrophobic core (Ac‐X₁KFEFKFE‐NH₂and Ac‐(X_1,5KFE)‐NH₂peptides, X = Trp or Bip). Spectroscopic analysis by circular dichroism (CD) and Fourier transform infrared (FT‐IR) spectroscopy indicatedβ‐sheet formation for all variants. Self‐assembly rate increased with peptide hydrophobicity; increased molecular volume of the hydrophobic side chain groups did not appear to induce kinetic penalties on self‐assembly rates. Transmission electron microscopy (TEM) imaging indicated variation in fibril morphology as a function of amino acid in the X positions. This study confirms that hydrophobicity of amphipathic Ac‐(XKXE)₂‐NH₂peptides correlates to self‐assembly propensity and that the hydrophobic core of the resulting nanoribbon bilayers has a significant capacity to accommodate sterically demanding functional groups. These findings provide insight that may be used to guide the exploitation of self‐assembled amphipathic peptides as functional biomaterials. 

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5. Iterative Design Reveals Molecular Domain Relationships in Supramolecular Peptide–Drug Conjugates

   https://doi.org/10.1021/acs.biomac.4c00519  

   Sis, Matthew J; Liu, Dongping; Allen, Isabella; Webber, Matthew J (July 2024, Biomacromolecules)

   Supramolecular peptide-drug conjugates (sPDCs) are prepared by covalent attachment of a drug moiety to a peptide motif programmed for one-dimensional self-assembly, with subsequent physical entanglement of these fibrillar structures enabling formation of nanofibrous hydrogels. This class of prodrug materials presents an attractive platform for mass-efficient and site-specific delivery of therapeutic agents using a discrete single-component molecular design. However, a continued challenge in sPDC development is elucidating relationships between supramolecular interactions in their drug and peptide domains and the resultant impact of these domains on assembly outcomes and material properties. Inclusion of a saturated alkyl segment alongside the prodrug in the hydrophobic domain of sPDCs could relieve some of the necessity for ordered, prodrug-produg interactions. Accordingly, nine sPDCs are prepared here to iterate the design variables of amino acid sequence and hydrophobic prodrug/alkyl block design. All molecules spontaneously formed hydrogels under physiological conditions, indicating a less hindered thermodynamic path to self-assembly relative to previous prodrug-only designs. However, material studies on the supramolecular arrangement, formation, and mechanical properties of the resultant sPDC hydrogels, as well as their drug release profiles, showed complex relationships between the hydrophobic and peptide domains in the formation and function of the resulting assemblies. Together, these results indicate that sPDC material properties are intrinsically linked to holistic molecular design, with coupled contributions from their prodrug and peptide domains in directing properties of the emergent materials. 

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