Selective covalent capture of collagen triple helices with a minimal protecting group strategy

Yu, Le Tracy; Hartgerink, Jeffrey D.

doi:10.1039/d1sc06361h

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…Previous work with covalent capture demonstrated not only the utility of providing extra stability and specificity to the triple helix but also biological applications, orthogonal synthetic schemes, and mechanistic elucidation. [24][25][26]34,35 Here we extended our investigation of the scope of covalent capture to include reverse, noncanonical charge pairs between lysine and either glutamate or aspartate. The four supramolecular peptides that were characterized above in Table 1 were also prepared for covalent capture and are summarized in Table 3.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Recently, our lab has used the formation of isopeptide bonds in a covalent capture strategy to increase the thermal stability of triple helices and expand their application scope. − We extend this approach here by investigating the stabilization of noncanonical charge pairs by isopeptide amide bond formation. Covalent capture was successful, and interestingly, the overall stability for a covalently captured reverse charge imparts more stability than its canonical counterpart.…”

Section: Introductionmentioning

confidence: 99%

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Stabilization of Synthetic Collagen Triple Helices: Charge Pairs and Covalent Capture

Cole,

Yu,

Misiura

et al. 2023

Biomacromolecules

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Collagen mimetic peptides are composed of triple helices. Triple helical formation frequently utilizes charge pair interactions to direct protein assembly. The design of synthetic triple helices is challenging due to the large number of competing species and the overall fragile nature of collagen mimetics. A successfully designed triple helix incorporates both positive and negative criteria to achieve maximum specificity of the supramolecular assembly. Intrahelical charge pair interactions, particularly those involved in lysine–aspartate and lysine–glutamate pairs, have been especially successful both in driving helix specificity and for subsequent stabilization by covalent capture. Despite this progress, the important sequential and geometric relationships of charged residues in a triple helical context have not been fully explored for either supramolecular assembly or covalent capture stabilization. In this study, we compare the eight canonical axial and lateral charge pairs of lysine and arginine with glutamate and aspartate to their noncanonical, reversed charge pairs. These findings are put into the context of collagen triple helical design and synthesis.

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stabilization of Synthetic Collagen Triple Helices: Charge Pairs and Covalent Capture

Cole,

Yu,

Misiura

et al. 2023

Biomacromolecules

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“…Size exclusion chromatography (SEC) was used to characterize the oligomeric state of the soluble peptide assembles of SPA-Rat and SPA-Human. The octadecameric assembly previously derived from C1q peptides was used as a point of comparison 36 in addition to a collagen triple helix standard 45 and globular protein standards (Fig. S16).…”

Section: Introductionmentioning

confidence: 99%

Beyond the Triple Helix: Exploration of the Hierarchical Assembly Space of Collagen-like Peptides

Yu,

Kreutzberger,

Hancu

et al. 2024

Preprint

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The de novo design of self-assembling peptides has garnered significant attention in scientific research. While alpha-helical assemblies have been extensively studied, exploration of polyproline type II (PPII) helices, such as those found in collagen, remains relatively limited. In this study, we focused on understanding the sequence-structure relationship in hierarchical assemblies of collagen-like peptides, using defense collagen SP-A as a model. By dissecting the sequence derived from SP-A and synthesizing short collagen-like peptides, we successfully constructed a discrete bundle of hollow triple helices. Mutation studies pinpointed amino acid sequences, including hydrophobic and charged residues that are critical for oligomer formation. These insights guided the de novo design of collagen-like peptides, resulting in the formation of diverse quaternary structures, including discrete and heterogenous bundled oligomers, 2D nanosheets, and pH-responsive nanoribbons. Our study represents a significant advancement in the understanding and harnessing of collagen higher-order assemblies beyond the triple helix.

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Exploration of the hierarchical assembly space of collagen-like peptides beyond the triple helix

Yu,

Kreutzberger,

Bui

et al. 2024

Nat Commun

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Selective covalent capture of collagen triple helices with a minimal protecting group strategy

Abstract: A minimal protecting group strategy is developed to allow selective covalent capture of collagen-like triple helices. This allows stabilization of this critical fold while preserving charge–pair interactions critical for biological applications.

Cited by 3 publications

References 45 publications

Stabilization of Synthetic Collagen Triple Helices: Charge Pairs and Covalent Capture

Stabilization of Synthetic Collagen Triple Helices: Charge Pairs and Covalent Capture

Beyond the Triple Helix: Exploration of the Hierarchical Assembly Space of Collagen-like Peptides

Exploration of the hierarchical assembly space of collagen-like peptides beyond the triple helix

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