Collagen mimetic peptides: progress towards functional applications

Yu, S. Michael; Li, Yang; Kim, Daniel

doi:10.1039/c1sm05329a

Cited by 119 publications

(137 citation statements)

References 95 publications

(151 reference statements)

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“…5 Collagen-like peptides (CLPs), also known as collagen-mimetic peptides (CMPs), have recently been investigated as potential alternatives to collagen, as they can self-assemble and form triple helical nanofibers like collagen. [6][7][8][9][10][11][12][13][14] In order to stabilize the triple helices of CLPs, polymer templates that can link the three peptide chains together with sufficient flexibility to allow for proper packing of the chains with correct amino acid register have been tested. 7 More recent designs have used collagen peptides as the physical crosslinks for the polymer system through triple helix formation.…”

Section: Introductionmentioning

confidence: 99%

Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation

et al. 2016

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Extracellular matrix proteins like collagen promote regeneration as implants in clinical studies. However, collagens are large and unwieldy proteins, making small functional peptide analogs potentially ideal substitutes. Self-assembling collagen-like-peptides conjugated with PEG-maleimide were assembled into hydrogels. When tested pre-clinically as corneal implants in mini-pigs, they promoted cell and nerve regeneration, forming neo-corneas structurally and functionally similar to natural corneas. IntroductionResident stem cells capable of regeneration are present in almost every organ in the body but frequently cannot achieve the repair needed after damage by injury or disease. The limiting factor is often the extracellular matrix (ECM) surrounding the cells. During damage, the ECM is frequently replaced by scar tissue, which does not provide the required structural integrity and inhibits regeneration of functional tissue. 1 The replacement of scar tissue with ECM or biomaterials that mimic its structure and function could therefore promote regeneration. 1,2 Regenerating damaged tissues and organs, including corneas, could potentially mitigate the need for organ transplantation, which currently faces acute worldwide shortage and immune rejection issues. We have previously shown in human corneal transplantation clinical studies that cell-free corneal ECM mimics made from recombinant human collagen (RHC) stimulated regeneration of the human cornea, an organ that normally does not regenerate on its own. 3,4 However, RHC replicates human collagen, which, like many other ECM biopolymers, is comprised of large proteins and is difficult to manipulate. Smaller units of complex proteins, particularly those capable of self-assembly have been examined as controllable ECM mimics, as they can form a wide range of structures including nanofibres. 5 Collagen-like peptides (CLPs), also known as collagen-mimetic peptides (CMPs), have recently been investigated as potential alternatives to collagen, as they can self-assemble and form triple helical nanofibers like collagen. [6][7][8][9][10][11][12][13][14] In order to stabilize the triple helices of CLPs, polymer templates that can link the three peptide chains together with sufficient flexibility to allow for proper packing of the chains with correct amino acid register have been tested. 7 More recent designs have used collagen peptides as the physical crosslinks for the polymer system through triple helix formation. 6,7 CLPs and CLP-polymer systems have now been tested in vitro as engineered 3D scaffolds on their own, 8 conjugated to polyethylene glycol (PEG) backbones, 9-11 and complexed with bioactive factors 12,13 or localization agents such as gold nanoparticles. 14 However, the majority of studies have been confined to in vitro testing with cells.The trend in regenerative medicine is now towards the use of complex, naturally derived ECM macromolecules, as intact decellularised scaffolds or as processed and purified concentrated liquids or finely ground powder that are the...

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Section: Introductionmentioning

confidence: 99%

Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation

et al. 2016

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“…Previously, we discovered that small collagen mimetic peptides (CMPs, molecular weight: 2-3 kDa) capable of reversibly forming collagen triple helices are able to bind to type I collagen (8)(9)(10)(11). Binding was observed only when CMPs [ðProHypGlyÞ x , x ¼ 6, 7, and 10] in a thermally melted, single-strand form and not in folded trimeric form were allowed to fold by cooling in the presence of type I collagen fibers (9,10).…”

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confidence: 99%

Targeting collagen strands by photo-triggered triple-helix hybridization

Foss

Summerfield

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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175

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Collagen remodeling is an integral part of tissue development, maintenance, and regeneration, but excessive remodeling is associated with various pathologic conditions. The ability to target collagens undergoing remodeling could lead to new diagnostics and therapeutics as well as applications in regenerative medicine; however, such collagens are often degraded and denatured, making them difficult to target with conventional approaches. Here, we present caged collagen mimetic peptides (CMPs) that can be phototriggered to fold into triple helix and bind to collagens denatured by heat or by matrix metalloproteinase (MMP) digestion. Peptidebinding assays indicate that the binding is primarily driven by stereo-selective triple-helical hybridization between monomeric CMPs of high triple-helical propensity and denatured collagen strands. Photo-triggered hybridization allows specific staining of collagen chains in protein gels as well as photo-patterning of collagen and gelatin substrates. In vivo experiments demonstrate that systemically delivered CMPs can bind to collagens in bones, as well as prominently in articular cartilages and tumors characterized by high MMP activity. We further show that CMP-based probes can detect abnormal bone growth activity in a mouse model of Marfan syndrome. This is an entirely new way to target the microenvironment of abnormal tissues and could lead to new opportunities for management of numerous pathologic conditions associated with collagen remodeling and high MMP activity.A s the most abundant protein in mammals, collagens play a crucial role in tissue development and regeneration, and their structural or metabolic abnormalities are associated with debilitating genetic diseases and various pathologic conditions. Although collagen remodeling occurs during development and normal tissue maintenance, particularly for renewing tissues (e.g., bones), excess remodeling activity is commonly seen in tumors, arthritis, and many other chronic wounds. During collagen remodeling, large portions of collagens are degraded and denatured by proteolytic enzymes, which can be explored for diagnostic and therapeutic purposes. Since unstructured proteins are not ideal targets for rational drug design, library approaches have been employed to develop monoclonal antibody (1, 2) and peptide probes (3) that specifically bind to cryptic sites in collagen strands that become exposed when denatured. However, these probes suffer from poor pharmacokinetics (4), and/or low specificity, and binding affinity (5).We envisioned that triple helix, the hallmark structural feature of collagen, could provide a unique targeting mechanism for the denatured collagens. The triple helix is nearly exclusively seen in collagens except as small subdomains in a few noncollagen proteins (6). Considering its striking structural similarity to the DNA double helix in terms of multiplex formation by periodic interchain hydrogen bonds along the polymer backbone (6), we thought that a small peptide sequence with strong triple-helix prope...

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“…The prime example of this has been recent work in the study of developing synthetic collagen mimetic peptides (CMPs). 117,118 These short peptide strands mimic natural collagen's Xxx-Yyy-Gly repeating triplet. Here, short-chain polypeptides, consisting of approximately 24-36 amino acids, self-assemble into triple helices and can further mimic all stages of natural collagen's multi-hierarchical self-assembly.…”

Section: Collagen-mimetic Peptidesmentioning

confidence: 99%

Rational design of fiber forming supramolecular structures

Kumar

Wang

Kanahara

2016

Exp Biol Med (Maywood)

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Recent strides in the development of multifunctional synthetic biomimetic materials through the self-assembly of multi-domain peptides and proteins over the past decade have been realized. Such engineered systems have wide-ranging application in bioengineering and medicine. This review focuses on fundamental fiber forming a-helical coiled-coil peptides, peptide amphiphiles, and amyloid-based self-assembling peptides; followed by higher order collagen-and elastin-mimetic peptides with an emphasis on chemical / biological characterization and biomimicry.

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Collagen mimetic peptides: progress towards functional applications

Cited by 119 publications

References 95 publications

Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation

Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation

Targeting collagen strands by photo-triggered triple-helix hybridization

Rational design of fiber forming supramolecular structures

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