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Abstract A fragment‐based approach has proven successful in drug design and protein assemblies, yet its potential for constructing biomaterials from simple organic building blocks remains underexplored, particularly for self‐assembly in aqueous phases, where water disrupts intermolecular hydrogen bonding. To the best of our knowledge, this study introduces the first case of integrating fragments from self‐assembling molecules to design a small organic molecule that forms novel hierarchical nanotubes with polymorphism. The molecule's compact design incorporates three structural motifs derived from known nanotube assemblies, enabling a hierarchical assembly process: individual molecules with two conformations form dimers, which organize into hexameric units. These hexamers further assemble into nanotubes comprising 2‐, 5‐, and 6‐protofilament fibers. The nanofibers share a nearly identical asymmetric unit – a hexameric triangular plate – with similar axial and lateral interfaces. The lateral interface, involving interactions between phosphate groups and aromatic rings, exhibits plasticity, allowing slight rotational variations between adjacent units. This adaptability facilitates the formation of diverse nanofiber architectures, showcasing the flexibility of these systems in aqueous environments. By leveraging fragments of self‐assembling molecules, this work demonstrates a straightforward strategy that combines conformational flexibility and self‐assembling fragments to construct advanced supramolecular biomaterials from small organic building blocks in aqueous settings.
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Using Self-Assembling Peptides to Integrate Biomolecules into Functional Supramolecular Biomaterials
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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- Award ID(s):
- 1743432
- PAR ID:
- 10109703
- Date Published:
- Journal Name:
- Molecules
- Volume:
- 24
- Issue:
- 8
- ISSN:
- 1420-3049
- Page Range / eLocation ID:
- 1450
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/molecules24081450
