Controlling the diameters of nanotubes represents a major challenge in nanostructures self‐assembled from templating molecules. Here, two series of bolaform hexapeptides are designed, with Set I consisting of Ac‐KI4K‐NH2, Ac‐KI3NleK‐NH2, Ac‐KI3LK‐NH2and Ac‐KI3TleK‐NH2, and Set II consisting of Ac‐KI3VK‐NH2, Ac‐KI2V2K‐NH2, Ac‐KIV3K‐NH2and Ac‐KV4K‐NH2. In Set I, substitution for Ile in the C‐terminal alters its side‐chain branching, but the hydrophobicity is retained. In Set II, the substitution of Val for Ile leads to the decrease of hydrophobicity, but the side‐chain β‐branching is retained. The peptide bolaphiles tend to form long nanotubes, with the tube shell being composed of a peptide monolayer. Variation in core side‐chain branching and hydrophobicity causes a steady shift of peptide nanotube diameters from more than one hundred to several nanometers, thereby achieving a reliable control over the underlying molecular self‐assembling processes. Given the structural and functional roles of peptide tubes with varying dimensions in nature and in technological applications, this study exemplifies the predictive templating of nanostructures from short peptide self‐assembly.
Amphipathic peptides with amino acids arranged in alternating patterns of hydrophobic and hydrophilic residues efficiently self‐assemble into
- NSF-PAR ID:
- 10449016
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Peptide Science
- Volume:
- 27
- Issue:
- 9
- ISSN:
- 1075-2617
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Self‐assembled peptides are an emerging family of biomaterials that show great promise for a range of biomedical and biotechnological applications. Introducing and tuning the pH‐responsiveness of the assembly is highly desirable for improving their biological activities. Inspired by proteins with internal ionizable residues, we report a simple but effective approach to constructing pH‐responsive peptide assembly containing unnatural ionic amino acids with an aliphatic tertiary amine side chain. Through a combined experimental and computational investigation, we demonstrate that these residues can be accommodated and stabilized within the internal hydrophobic compartment of the peptide assembly. The hydrophobic microenvironment shifts their pKasignificantly from a basic pH typically found for free amines to a more biologically relevant pH in the weakly acidic range. The pH‐induced ionization and ionization‐dependent self‐assembly and disassembly are thoroughly investigated and correlated with the biological activity of the assembly. This new approach has unique advantages in tuning the pH‐responsiveness of self‐assembled peptides across a large pH range in a complex biological environment. We anticipate the ionizable amino acids developed here can be widely applicable to the synthesis and self‐assembly of many amphiphilic peptides with endowed pH‐responsive properties to enhance their biological activities toward applications ranging from targeted therapeutic delivery to proton transport.
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Side‐Chain Chemistry Governs Hierarchical Order of Charge‐Complementary β‐sheet Peptide Coassemblies
Abstract Self‐assembly of proteinaceous biomolecules into functional materials with ordered structures that span length scales is common in nature yet remains a challenge with designer peptides under ambient conditions. This report demonstrates how charged side‐chain chemistry affects the hierarchical co‐assembly of a family of charge‐complementary β‐sheet‐forming peptide pairs known as CATCH(X+/Y−) at physiologic pH and ionic strength in water. In a concentration‐dependent manner, the CATCH(6K+) (Ac‐KQKFKFKFKQK‐Am) and CATCH(6D−) (Ac‐DQDFDFDFDQD‐Am) pair formed either β‐sheet‐rich microspheres or β‐sheet‐rich gels with a micron‐scale plate‐like morphology, which were not observed with other CATCH(X+/Y−) pairs. This hierarchical order was disrupted by replacing D with E, which increased fibril twisting. Replacing K with R, or mutating the N‐ and C‐terminal amino acids in CATCH(6K+) and CATCH(6D−) to Qs, increased observed co‐assembly kinetics, which also disrupted hierarchical order. Due to the ambient assembly conditions, active CATCH(6K+)‐green fluorescent protein fusions could be incorporated into the β‐sheet plates and microspheres formed by the CATCH(6K+/6D−) pair, demonstrating the potential to endow functionality.
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Side‐Chain Chemistry Governs Hierarchical Order of Charge‐Complementary β‐sheet Peptide Coassemblies
Abstract Self‐assembly of proteinaceous biomolecules into functional materials with ordered structures that span length scales is common in nature yet remains a challenge with designer peptides under ambient conditions. This report demonstrates how charged side‐chain chemistry affects the hierarchical co‐assembly of a family of charge‐complementary β‐sheet‐forming peptide pairs known as CATCH(X+/Y−) at physiologic pH and ionic strength in water. In a concentration‐dependent manner, the CATCH(6K+) (Ac‐KQKFKFKFKQK‐Am) and CATCH(6D−) (Ac‐DQDFDFDFDQD‐Am) pair formed either β‐sheet‐rich microspheres or β‐sheet‐rich gels with a micron‐scale plate‐like morphology, which were not observed with other CATCH(X+/Y−) pairs. This hierarchical order was disrupted by replacing D with E, which increased fibril twisting. Replacing K with R, or mutating the N‐ and C‐terminal amino acids in CATCH(6K+) and CATCH(6D−) to Qs, increased observed co‐assembly kinetics, which also disrupted hierarchical order. Due to the ambient assembly conditions, active CATCH(6K+)‐green fluorescent protein fusions could be incorporated into the β‐sheet plates and microspheres formed by the CATCH(6K+/6D−) pair, demonstrating the potential to endow functionality.
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