Anticoagulant supramolecular-structured polymers: Synthesis and anti coagulant activity of taurine-conjugated carboxyethylester-polyrotaxanes

Joung, Yoon Ki; Sengoku, Yoichi; Ooya, Tooru; Парк, Ки Донг; Yui, Nobuhiko

doi:10.1016/j.stam.2005.03.013

Cited by 20 publications

(22 citation statements)

References 25 publications

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“…16 Other work has verified this point by showing that the spacing of the negative charges in heparin-mimicking polymers is important for protein binding. 33 Spacing of the negative charges throughout p(SS- co -PEGMA) 81 is the most likely reason that the 81% polymer performed better than other percentages in the binding assays. Furthermore, heparin has a very high negative charge to size ratio, which contributes greatly to its binding properties.…”

Section: Resultsmentioning

confidence: 99%

Structure activity relationship of heparin mimicking polymer p(SS-co-PEGMA): effect of sulfonation and polymer size on FGF2-receptor binding

Paluck

Maynard

2017

Polym. Chem.

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Fibroblast growth factor-2 (FGF2) is a heparin binding protein that plays a role in a range of biological functions such as wound healing and bone regeneration. Heparin, a highly sulfated glycosaminoglycan, is required for FGF2 to bind to its receptor. Therefore, polymeric mimics of heparin are widely studied for their ability to manipulate FGF2-induced biological interactions. It is known that altering the degree of sulfonated monomer incorporation and size of heparin-mimicking polymers can affect protein-receptor binding. To elucidate the relationship between degree of sulfonation and receptor binding for the heparin-mimicking polymer, poly(styrene sulfonate-co-poly(ethylene glycol) methyl ether methacrylate) (p(SS-co-PEGMA)) a library was synthesized to contain nine polymers with degrees of sulfonation ranging from 0-100%. Kinetics of the polymerization was evaluated and reactivity ratios compared to literature results. These polymers were then tested for their ability to enhance FGF2 binding with its receptor as both covalent conjugates and as excipients. In a receptor based enzyme-linked immunosorbant assay (ELISA), as well as a cell-based study, the polymer with 81% SS incorporation enhanced receptor binding compared to FGF2 alone, and to a greater extent than the other polymers. Therefore, another library of polymers was prepared maintaining the degree of sulfonation at 81% and changing the size from 41 to 390 monomer repeat units. The polymers were again tested in receptor based ELISA and cell studies, and all of the different sizes performed similarly, except for degree of polymerization 295 and 390, which had reduced response in the cellular assay. These results provide important information for the use of pSS-co-PEGMA as a potential heparin-mimicking therapeutic.

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Section: Resultsmentioning

confidence: 99%

Structure activity relationship of heparin mimicking polymer p(SS-co-PEGMA): effect of sulfonation and polymer size on FGF2-receptor binding

Paluck

Maynard

2017

Polym. Chem.

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“…The PEG/α‐CD‐based PRX capped with N ‐benzyloxycarbonyl‐l‐tyrosine was synthesized according to a previous report . The sulfonated PRXs (S‐PRXs) with the various numbers of sulfonate groups were synthesized from the PEG/α‐CD‐based PRX (the number of threading α‐CDs: 29.2; M n of PEG axle: 4,550; M n of PRX: 33,500) according to the previous report with slight modification (Figure ) . A typical procedure for synthesis of S‐PRX (26S‐PRX in Table ) is described as follows.…”

Section: Methodsmentioning

confidence: 99%

Supramolecular Polyelectrolyte Complexes of Bone Morphogenetic Protein‐2 with Sulfonated Polyrotaxanes to Induce Enhanced Osteogenic Differentiation

Terauchi

Ikeda

Nishida

et al. 2015

Macromolecular Bioscience

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Although bone morphogenetic protein-2 (BMP-2) has received considerable attention because of its strong osteoinductivity, the clinical application of BMP-2 is limited due to its degradation and deactivation under physiological conditions. Negatively charged heparin is known to form polyelectrolyte complexes with BMP-2 to prevent deactivation and enhance the osteoinduction capability of BMP-2. Herein, we report the sulfonated polyrotaxanes (S-PRX) composed of α-cyclodextrin threaded onto a linear polymer for the protection of BMP-2 through the polyelectrolyte complex formation. When MC3T3-E1 osteoprogenitor cells were treated with the S-PRX/BMP-2 complexes, significantly high alkaline phosphatase production and mineralized matrix deposition were observed compared with that of free BMP-2 and heparin/BMP-2 complexes. Note that the S-PRXs showed negligible anticoagulant activity and cytotoxicity, whereas heparin showed strong anticoagulant activity. Accordingly, the S-PRXs are promising candidates for enhanced osteoinduction ability of BMP-2 without toxicity and anticoagulant activity and could contribute to clinical bone regeneration.

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“…Carboxilate polyrotaxane (PRx-Sa) was prepared according to previous reports. 12,18,19 TA-terminated PEG (TPEG) was synthesized using a carbamate linkage. Dried PEG was completely dissolved in DMF and then reacted with NPC in the presence of TEA.…”

Section: Methodsmentioning

confidence: 99%

RGD-conjugated In Situ forming hydrogels as cell-adhesive injectable scaffolds

et al. 2011

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In this study, a bioactive hydrogel was prepared from a chitosan derivative and Arg-Gly-Asp (RGD)-conjugated polypseudorotaxane, which is a cell-adhesive extracellular matrix. Chitosan was modified with 4-hydroxy phenyl acetic acid to obtain a water-soluble product for enzymatic cross-linking. Tyramine-terminated polypseudorotaxane (PRx) was prepared from the inclusion complex of a tyramine-terminated poly(ethylene glycol) backbone, and α-cyclodextrin (α-CD). Gly-Arg-Gly-Asp-Ser (GRGDS) was conjugated to the PRx using 4-nitrophenyl chloroformate (NPC) and partially carboxylated with succinic anhydride. The structure of the PRx-RGD and 4-hydroxylphenylacetamide chitosan (CHPA) was characterized by 1 H NMR and FTIR spectroscopy. The RGD content in PRx-RGD was determined to be 0.19%. PRx-RGD and CHPA solution was crosslinked to form a bioactive hydrogel in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ), which exhibited rapid gelation (~20 sec). An in vitro cell culture was carried out with L929 mouse fibroblasts for 1 and 3 days. The results showed that fibroblasts adhered better and appeared to be more biocompatible on the RGD-conjugated hydrogel than the hydrogel without RGD. The combined results highlight the potential use of this bioactive hydrogel as an injectable scaffold in tissue engineering applications.

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Anticoagulant supramolecular-structured polymers: Synthesis and anti coagulant activity of taurine-conjugated carboxyethylester-polyrotaxanes

Cited by 20 publications

References 25 publications

Structure activity relationship of heparin mimicking polymer p(SS-co-PEGMA): effect of sulfonation and polymer size on FGF2-receptor binding

Structure activity relationship of heparin mimicking polymer p(SS-co-PEGMA): effect of sulfonation and polymer size on FGF2-receptor binding

Supramolecular Polyelectrolyte Complexes of Bone Morphogenetic Protein‐2 with Sulfonated Polyrotaxanes to Induce Enhanced Osteogenic Differentiation

RGD-conjugated In Situ forming hydrogels as cell-adhesive injectable scaffolds

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