Promotion of human platelet adhesion and aggregation by a synthetic, triple-helical “mini-collagen”.

Rao, G. H. R.; Fields, Cynthia G.; White, James G.; Fields, Gregg B.

doi:10.1016/s0021-9258(17)36732-7

Cited by 29 publications

(10 citation statements)

References 36 publications

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“…As reported previously, there is another case of a branched triple-helical peptide that aggregated. At least three molecules had complexed to form aggregates, as shown by SE chromatography (12) and rotary shadowing microscopy (40). The cooperative melting transition of this peptide seems to be determined by a molecularity greater than 2.…”

Section: Discussionmentioning

confidence: 89%

“…The data demonstrate that at 4 °C the peptides are present as dimers, and there is no aggregation of the peptides, increasing temperature from 4 to 35 °C. Another branched triple-helical peptide, comprising the R1(IV) 1263-1277 sequence, was shown to aggregate (40), and this aggregation, in contrast to the aggregation of the PP*G(6-8) peptides, was induced by increasing temperature (12). SE chromatography at 4 and 35 °C yielded molecular weights of 11.6 and 36 kD, respectively, indicating at 4 °C the monomeric molecule and at 35 °C the association of three molecules to a trimer.…”

Section: Discussionmentioning

confidence: 99%

“…(ii) Alternatively, branch synthesis was started with the FmocGlyTentaGel R PHB resin (substitution level: 0.18 mmol/g). 34.5 mg of FmocTyr(tBu) (75 µmol), 40 (3 × 8.34 µmol) free amino groups, was performed as outlined above. Incorporation of the type III collagen-specific sequence GlyProProGlyLysAsnGlyGluThrGlyProGlnGly onto the branched peptide resin was achieved by single couplings for residues 13-7 and double couplings for residues 6-1.…”

Section: Synthesis Of Tripeptides (I)mentioning

confidence: 99%

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Synthesis and Folding of Native Collagen III Model Peptides

et al. 1999

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Solid-phase synthesis of triple-helical peptides, including native collagen III sequences, was started with a trimeric branch, based upon the lysine dipeptide [Fields, C. G., Mickelson, D. J., Drake, S. L., McCarthy, J. B., and Fields, G. B. (1993) J. Biol. Chem. 268, 14153-14160]. Branch synthesis was modified, using TentaGel R as resin, p-hydroxybenzyl alcohol (HMP) as linker, Dde as N(epsilon)-protective group, and HATU/HOAT as coupling reagent. Three homotrimeric sequences, each containing the Gly 606-Gly 618 portion of human type III collagen, were added to the amino functions of the branch. The final incorporation of GlyProHyp triplets, stabilizing the collagen III triple helix, was performed by using protected GlyProHyp tripeptides, each containing tert-butylated hydroxyproline [P(tBu)] instead of hydroxyproline (P). Among the protected tripeptides FmocP(tBu)PG, FmocPP(tBu)G, and FmocGPP(tBu), prepared manually on a chlorotrityl resin, incorporation of FmocPP(tBu)Gly was best suited for synthesis of large and stable peptides, such as PPG(8), containing 8 (PPG)(3) trimers (115 residues, 10 610 Da). The structures of five peptides, differing from each other by the type and number of the triplets incorporated, were verified by MALDI-TOF-MS. Their conformations and thermodynamic data were studied by circular dichroism and differential scanning calorimetry. Except for PPG(8), containing 8 (PPG)(3) trimers with hydroxyproline in the X position and adopting a polyproline II structure, all peptides were triple-helical in 0.1 M acetic acid and their thermal stabilities ranged from t(1/2) = 39. 4 to t(1/2) = 62.5 degrees C, depending on the identity and number of the triplets used. Similar values of the van't Hoff enthalpy, DeltaH(vH), derived from melting curves, and the calorimetric enthalpy, DeltaH(cal), obtained from heat capacity curves, indicate a cooperative ratio of CR = DeltaH(vH)/DeltaH(cal) = 1, establishing a two-state process for unfolding of THP(III) peptides. The independence of the transition temperatures t(1/2) on peptide concentration as well as equilibrium centrifugation data indicate monomolecular dimer(f) to dimer(u) (F(2) <--> U(2)) transitions and, in addition, bimolecular dimer(f) to monomer(u) transitions (F(2) <--> 2U). The dominance of the concentration-independent monomolecular reaction over the concentration-dependent bimolecular reaction makes thermal unfolding of THP(III) peptides appear to be monomolecular. If one designates the molecularity described by the term pseudomonomolecular, unfolding of the dimeric peptides PPG(6-8) follows a two-state, pseudomonomolecular reaction.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Synthesis Of Tripeptides (I)mentioning

confidence: 99%

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Synthesis and Folding of Native Collagen III Model Peptides

et al. 1999

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“…The collagen-model triple-helix has also been used for functional protein design. Synthetic triple-helical proteins have incorporated type IV collagen sequences that promote adhesion and spreading of tumor cells, , type I collagen sequences that promote adhesion of fibroblasts, type III or IV collagen sequences that induce the aggregation of platelets, and macrophage scavenger receptor sequences that bind acetylated low-density lipoproteins …”

Section: Introductionmentioning

confidence: 99%

Self-Assembling Amphiphiles for Construction of Protein Molecular Architecture

et al. 1996

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Peptide-amphiphiles with collagen-model head groups and dialkyl chain tails have been synthesized and shown to self-assemble into highly ordered polyPro II like triple-helical structures when dissolved in aqueous subphases. Evidence for this self-assembly process has been obtained from (a) compression of stable peptide-amphiphile monolayers to molecular areas comparable with triple-helical areas, (b) circular dichroism spectra and melting curves characteristic of triple-helices, and (c) two-dimensional NMR spectra indicative of stable triple-helical structure at low temperatures and melted triple-helices at high temperatures. The thermal stability of the collagen-like structure in the peptide-amphiphile is substantially higher (ΔT m = 15−20 °C) than that of peptides without lipidation. The assembly process driven by the hydrophobic tail may provide a general method for creating well-defined protein molecular architecture using a minimalist peptide-based approach.

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“…In addition to studying the structure and stability of CMPs as models for natural collagen, a number of research groups have developed new types of CMPs and CMP derivatives that can potentially be used for biomedical applications. These include (i) novel CMPs with new supramolecular architecture 19,20 or CMPs tailored toward modulating the stability or composition of the triple helices, 21,22 (ii) CMPs that can self-assemble into higher order structures, [23][24][25] (iii) CMPs that can be triggered to fold or assemble into higher order structures, [26][27][28] (iv) CMPs that incorporate cell interactive sites as well as those that can specifically bind to natural collagen, [29][30][31][32][33][34] and (v) PEG-based hydrogels that display CMPs for facile assimilation with cellular ECMs. [35][36][37] A significant portion of work in these applications is still at a fundamental level and the feasibility of CMP use in biomedical applications needs to be verified; however recent research activity in the design and synthesis of new CMPs suggests that the collagen triple helix has become a promising structural motif for engineering self-assembled, hierarchical constructs similar to natural tissue scaffolds which may exhibit unique or enhanced biological activity.…”

Section: Daniel Kimmentioning

confidence: 99%

Collagen mimetic peptides: progress towards functional applications

2011

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Traditionally, collagen mimetic peptides (CMPs) have been used for elucidating the structure of the collagen triple helix and the factors responsible for its stabilization. The wealth of fundamental knowledge on collagen structure and cell-extracellular matrix (ECM) interactions accumulated over the past decades has led to a recent burst of research exploring the potential of CMPs to recreate the higher order assembly and biological function of natural collagens for biomedical applications. Although a large portion of such research is still at an early stage, the collagen triple helix has become a promising structural motif for engineering self-assembled, hierarchical constructs similar to natural tissue scaffolds which are expected to exhibit unique or enhanced biological activities. This paper reviews recent progress in the field of collagen mimetic peptides that bears both direct and indirect implications to engineering collagen-like materials for potential biomedical use. Various CMPs and collagen-like proteins that mimic either structural or functional characteristics of natural collagens are discussed with particular emphasis on providing helpful information to bioengineers and biomaterials scientists interested in collagen engineering.

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Promotion of human platelet adhesion and aggregation by a synthetic, triple-helical “mini-collagen”.

Cited by 29 publications

References 36 publications

Synthesis and Folding of Native Collagen III Model Peptides

Synthesis and Folding of Native Collagen III Model Peptides

Self-Assembling Amphiphiles for Construction of Protein Molecular Architecture

Collagen mimetic peptides: progress towards functional applications

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