Cyclic Peptide Mimetic of Damaged Collagen

Ellison, Aubrey J.; Tanrikulu, I. Caglar; Dones, Jesús M.; Raines, Ronald T.

doi:10.1021/acs.biomac.0c00103

Cited by 14 publications

(21 citation statements)

References 47 publications

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“…21 As a CMP, we chose (PPG)7 because of its simplicity and demonstrated efficacy in relevant contexts in vitro, ex vivo, and in vivo. 26,28,29,32,33 In its selection, LTGKNFPMFHRN (Tβrl) was displayed as a fusion to the N-terminus of the PIII coat protein of phage. 21 We mimicked this display by conjugating Tβrl to the N-terminus of CMP.…”

Section: Resultsmentioning

confidence: 99%

“…[23][24][25] We and others have reported on the use of collagenmimetic peptides (CMPs) to anchor probes and growth factors in damaged or abnormal collagen. [26][27][28][29][30][31][32][33][34] Here, we use a CMP conjugate to immobilize a peptidic ligand for TGF-β receptors in wound beds of mice. Our intent is to cluster cell-surface TβRI and TβRII and thereby enhance the sensitivity of cells to circulating TGF-β (Figure 1B).…”

Section: Introductionmentioning

confidence: 99%

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Bifunctional Peptide that Anneals to Damaged Collagen and Clusters TGF-β Receptors Enhances Wound Healing

Chattopadhyay

Teixeira

Kiessling

et al. 2021

Preprint

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Transforming growth factor-β (TGF-β) plays important roles in wound healing. The activity of TGF-β is initiated upon binding of the growth factor to extracellular domains of its receptors. We sought to facilitate activation by clustering these extracellular domains. To do so, we used a known peptide that binds to TGF-β receptors without diminishing their affinity for TGF-β. We conjugated this peptide to a collagen-mimetic peptide that can anneal to damaged collagen in a wound bed. We find that the conjugate enhances collagen deposition and wound closure in mice in a manner consistent with the clustering of TGF-β receptors. This strategy provides a means to upregulate the TGF-β signaling pathway without adding exogenous TGF-β and could inspire means to treat severe wounds.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bifunctional Peptide that Anneals to Damaged Collagen and Clusters TGF-β Receptors Enhances Wound Healing

Chattopadhyay

Teixeira

Kiessling

et al. 2021

Preprint

Self Cite

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“…Such CHPs can potentially be used to detect bacterial infection at the wound bed. Another modified CHP with the sequence Cy5-G(SG) 2 -(fOG) 7 was used to assess the wound healing and tissue remodeling process in injured human skin, the burned damages in tissues, and the abnormal ECM in bone associated with developmental detects [ 149 , 150 , 151 , 152 ].…”

Section: Collagen Mimetic Peptides By Chemical Synthesismentioning

confidence: 99%

Collagen Mimetic Peptides

Kirchner

2021

Bioengineering

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Since their first synthesis in the late 1960s, collagen mimetic peptides (CMPs) have been used as a molecular tool to study collagen, and as an approach to develop novel collagen mimetic biomaterials. Collagen, a major extracellular matrix (ECM) protein, plays vital roles in many physiological and pathogenic processes. Applications of CMPs have advanced our understanding of the structure and molecular properties of a collagen triple helix—the building block of collagen—and the interactions of collagen with important molecular ligands. The accumulating knowledge is also paving the way for developing novel CMPs for biomedical applications. Indeed, for the past 50 years, CMP research has been a fast-growing, far-reaching interdisciplinary field. The major development and achievement of CMPs were documented in a few detailed reviews around 2010. Here, we provided a brief overview of what we have learned about CMPs—their potential and their limitations. We focused on more recent developments in producing heterotrimeric CMPs, and CMPs that can form collagen-like higher order molecular assemblies. We also expanded the traditional view of CMPs to include larger designed peptides produced using recombinant systems. Studies using recombinant peptides have provided new insights on collagens and promoted progress in the development of collagen mimetic fibrillar self-assemblies.

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“…Beyond synthesis, CMPs, as well as other peptides that assemble near room temperature, can present some challenges during purification . For example, the presence of aggregates during separation with high performance liquid chromatography (HPLC) impacts the ability to separate individual peptides and thereby remove sequences with deletions. , Self-assembling peptide purification with HPLC may be improved with a number of modifications, including sonication of the peptide solution prior to injection onto the column, the addition of chaotropic agents [such as trifluoroacetic acid (TFA)] to disrupt aggregation, and decreasing the mobile phase gradient for improved peak separation . Use of a column heater can be particularly beneficial for HPLC purification of CMPs and other thermally responsive assembling peptides, as it allows for separation above the temperature at which peptides thermally unfold and is simple to implement. ,, To ensure full “melting”, or thermal unfolding of assembling peptides, some researchers include an additional step of holding the peptide solution at a high temperature prior to HPLC separation at an elevated temperature .…”

Section: Introductionmentioning

confidence: 99%

Rapid Production of Multifunctional Self-Assembling Peptides for Incorporation and Visualization within Hydrogel Biomaterials

Ford

Kloxin

2021

ACS Biomater. Sci. Eng.

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Peptides are of continued interest for therapeutic applications, from soluble and immobilized ligands that promote desired binding or uptake to self-assembled supramolecular structures that serve as scaffolds in vitro and in vivo. These applications require efficient and scalable synthetic approaches because of the large amounts of material that often are needed for studies of bulk material properties and their translation. In this work, we establish new methods for the synthesis, purification, and visualization of assembling peptides, with a focus on multifunctional collagen mimetic peptides (mfCMPs) relevant for formation and integration within hydrogel-based biomaterials. First, a methodical approach useful for the microwave-assisted synthesis of assembling peptide sequences prone to deletions was established, beginning with the identification of the deleted residues and their locations and followed by targeted use of dual chemistry couplings for those specific residues. Second, purification techniques that integrate the principles of heating and ion displacement with traditional chromatography and dialysis were implemented to improve separation and isolation of the desired multifunctional peptide product, which contained blocks for thermoresponsiveness and ionic interactions. Third, an approach for fluorescent labeling of these mfCMPs, which is orthogonal to their assembly and their covalent incorporation into a bulk hydrogel material, was established, allowing visualization of the resulting hierarchical fibrillar structures in three dimensions within hydrogels using confocal microscopy. The methods presented in this work allow the production of multifunctional peptides in scalable quantities and with minimal deletions, enabling future studies for better understanding of composition−structure−property relationships and for translating these biomaterials into a range of applications. Although mfCMPs are the focus of this work, the methods demonstrated could prove useful for other assembling peptide systems and for the production of peptides more broadly for therapeutic applications.

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Cyclic Peptide Mimetic of Damaged Collagen

Cited by 14 publications

References 47 publications

Bifunctional Peptide that Anneals to Damaged Collagen and Clusters TGF-β Receptors Enhances Wound Healing

Bifunctional Peptide that Anneals to Damaged Collagen and Clusters TGF-β Receptors Enhances Wound Healing

Collagen Mimetic Peptides

Rapid Production of Multifunctional Self-Assembling Peptides for Incorporation and Visualization within Hydrogel Biomaterials

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