Syntheses of sulfated glycopolymers and analyses of their BACE-1 inhibitory activity

Nishimura, Y.; Shudo, Hiroki; Seto, Hirokazu; Hoshino, Yu; Miura, Yoshiko

doi:10.1016/j.bmcl.2013.09.057

Cited by 15 publications

(14 citation statements)

References 39 publications

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“…18 Miura and co-workers demonstrated an inhibitory effect of GAG mimetic glycopolymers on Alzheimer's β-secretase, playing an important role in Alzheimer's disease. 19 A first study testing for the antiviral activity of sulfated glycopolymers was reported by Tengdelius and co-workers who introduced polymethacrylamides with pendant sulfated α-L-fucosides that exhibited inhibitory activity against HSV-1 similar to that of fucoidan, a natural anionic polysaccharide produced in algae. 20 In this study, we synthesize and apply a series of sulfated glycomimetic oligomers and polymers to test for their antiviral potential.…”

Section: ■ Introductionmentioning

confidence: 99%

“…For example, glycopolymer GAG mimetics as introduced by Hsieh-Wilson and co-workers were studied as anticoagulants showing activity comparable to that of commercial products such as Arixtra . Miura and co-workers demonstrated an inhibitory effect of GAG mimetic glycopolymers on Alzheimer’s β-secretase, playing an important role in Alzheimer’s disease . A first study testing for the antiviral activity of sulfated glycopolymers was reported by Tengdelius and co-workers who introduced polymethacrylamides with pendant sulfated α- l -fucosides that exhibited inhibitory activity against HSV-1 similar to that of fucoidan, a natural anionic polysaccharide produced in algae …”

Section: Introductionmentioning

confidence: 99%

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Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers

et al. 2020

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In this work, we investigate the potential of highly sulfated synthetic glycomimetics to act as inhibitors of viral binding/infection. Our results indicate that both long-chain glycopolymers and short-chain glycooligomers are capable of preventing viral infection. Notably, glycopolymers efficiently inhibit Human Papillomavirus (HPV16) infection in vitro and maintain their antiviral activity in vivo, while the glycooligomers exert their inhibitory function post attachment of viruses to cells. Moreover, when we tested the potential for broader activity against several other human pathogenic viruses, we observed broad-spectrum antiviral activity of these compounds beyond our initial assumptions. While the compounds tested displayed a range of antiviral efficacies, viruses with rather diverse glycan specificities such as Herpes Simplex Virus (HSV), Influenza A Virus (IAV), and Merkel Cell Polyomavirus (MCPyV) could be targeted. This opens new opportunities to develop broadly active glycomimetic inhibitors of viral entry and infection.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers

et al. 2020

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“…By altering the placement and number of sulfates on sugar side chains in glycopolymers, certain biological pathways can be targeted. 22,23 …”

Section: Introductionmentioning

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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“…118 (e) 3,4,6-Sulfoglucosamines copolymerized by free radical polymerization by Miura and co-workers. 121 …”

Section: Heparin-mimicking Polymersmentioning

confidence: 99%

“…By varying the sulfation pattern on the pendant glucosamines from 3-sulfo, 4-sulfo, 6-sulfo and 3,4,6-sulfo, the authors found that polymers containing 3,4,6-sulfo pendant sugars significantly inhibited BACE-1 activity (a protease known to be involved in the pathogenesis of AD), while the 6-sulfo modestly inhibited (Figure 4e). 121 It was later shown that polymers containing 6-sulfo pendant sugars reduced amyloid fibril formation. 122 Interestingly, polymers with modest sugar contents inhibited amyloid β fibril formation more effectively than polymers with high sugar contents.…”

Section: Carboxymethyl Benzylamide Sulfonate Dextrans (Cmdbs)mentioning

confidence: 99%

Heparin-Mimicking Polymers: Synthesis and Biological Applications

2016

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Heparin is a naturally occurring, highly sulfated polysaccharide that plays a critical role in a range of different biological processes. Therapeutically, it is mostly commonly used as an injectable solution as an anticoagulant for a variety of indications, although it has also been employed in other forms such as coatings on various biomedical devices. Due to the diverse functions of this polysaccharide in the body, including anticoagulation, tissue regeneration, anti-inflammation, and protein stabilization, and drawbacks of its use, analogous heparin-mimicking materials are also widely studied for therapeutic applications. This review focuses on one type of these materials, namely, synthetic heparin-mimicking polymers. Utilization of these polymers provides significant benefits compared to heparin, including enhancing therapeutic efficacy and reducing side effects as a result of fine-tuning heparin-binding motifs and other molecular characteristics. The major types of the various polymers are summarized, as well as their applications. Because development of a broader range of heparin-mimicking materials would further expand the impact of these polymers in the treatment of various diseases, future directions are also discussed.

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Syntheses of sulfated glycopolymers and analyses of their BACE-1 inhibitory activity

Cited by 15 publications

References 39 publications

Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers

Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers

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

Heparin-Mimicking Polymers: Synthesis and Biological Applications

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