Heparan sulphate, its derivatives and analogues share structural characteristics that can be exploited, particularly in inhibiting microbial attachment

Rudd, Timothy R.; Hughes, Ashley J.; Holman, Joseph; Solari, Valeria; Ferreira, Eliane de Oliveira; Domingues, R.M. Cavalcante Pilotto; Yates, Edwin A.

doi:10.1590/s0100-879x2012007500048

Cited by 5 publications

(2 citation statements)

References 44 publications

(44 reference statements)

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“…Cell-surface HS is used by many microbial pathogens, whether bacteria, viruses or parasites, as a host attachment factor [ 16 , 54 ]. This includes both Gram +ve and Gram −ve bacteria that are the most common infections leading to sepsis.…”

Section: Non-anticoagulant Action Of Heparin and Sepsismentioning

confidence: 99%

Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment

Hogwood

Gray

2023

Pharmaceuticals

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Sepsis is a life-threatening hyperreaction to infection in which excessive inflammatory and immune responses cause damage to host tissues and organs. The glycosaminoglycan heparan sulphate (HS) is a major component of the cell surface glycocalyx. Cell surface HS modulates several of the mechanisms involved in sepsis such as pathogen interactions with the host cell and neutrophil recruitment and is a target for the pro-inflammatory enzyme heparanase. Heparin, a close structural relative of HS, is used in medicine as a powerful anticoagulant and antithrombotic. Many studies have shown that heparin can influence the course of sepsis-related processes as a result of its structural similarity to HS, including its strong negative charge. The anticoagulant activity of heparin, however, limits its potential in treatment of inflammatory conditions by introducing the risk of bleeding and other adverse side-effects. As the anticoagulant potency of heparin is largely determined by a single well-defined structural feature, it has been possible to develop heparin derivatives and mimetic compounds with reduced anticoagulant activity. Such heparin mimetics may have potential for use as therapeutic agents in the context of sepsis.

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Section: Non-anticoagulant Action Of Heparin and Sepsismentioning

confidence: 99%

Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment

Hogwood

Gray

2023

Pharmaceuticals

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“…Therapeutic GAG-like molecules can come from different natural sources, including mammalian tissues, non-mammalian origins such as invertebrates, and synthetic GAG mimetics. These molecules can act both as agonist or antagonist either by interfering with endogenous GAGs or by forming complexes with protein ligand and/or receptors ( Rudd et al, 2012 ; Pomin, 2015 ). The possible role of GAG analogs in inhibiting pathogen interaction has been widely studied, especially in virus attachment and dissemination.…”

Section: Glycosaminoglycans As Therapeutic Targetsmentioning

confidence: 99%

Surface Proteoglycans as Mediators in Bacterial Pathogens Infections

et al. 2016

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Infectious diseases remain an important global health problem. The interaction of a wide range of pathogen bacteria with host cells from many different tissues is frequently mediated by proteoglycans. These compounds are ubiquitous complex molecules which are not only involved in adherence and colonization, but can also participate in other steps of pathogenesis. To overcome the problem of microbial resistance to antibiotics new therapeutic agents could be developed based on the characteristics of the interaction of pathogens with proteoglycans.

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Highly Efficient Multivalent 2D Nanosystems for Inhibition of Orthopoxvirus Particles

Ziem

Thien

Achazi

et al. 2016

Adv Healthcare Materials

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Efficient inhibition of cell-pathogen interaction to prevent subsequent infection is an urgent but yet unsolved problem. In this study, the synthesis and functionalization of novel multivalent 2D carbon nanosystems as well as their antiviral efficacy in vitro are shown. For this reason, a new multivalent 2D flexible carbon architecture is developed in this study, functionalized with sulfated dendritic polyglycerol, to enable virus interaction. A simple "graft from" approach enhances the solubility of thermally reduced graphene oxide and provides a suitable 2D surface for multivalent ligand presentation. Polysulfation is used to mimic the heparan sulfate-containing surface of cells and to compete with this natural binding site of viruses. In correlation with the degree of sulfation and the grafted polymer density, the interaction efficiency of these systems can be varied. In here, orthopoxvirus strains are used as model viruses as they use heparan sulfate for cell entry as other viruses, e.g., herpes simplex virus, dengue virus, or cytomegalovirus. The characterization results of the newly designed graphene derivatives demonstrate excellent binding as well as efficient inhibition of orthopoxvirus infection. Overall, these new multivalent 2D polymer nanosystems are promising candidates to develop potent inhibitors for viruses, which possess a heparan sulfate-dependent cell entry mechanism.

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Heparan sulphate, its derivatives and analogues share structural characteristics that can be exploited, particularly in inhibiting microbial attachment

Cited by 5 publications

References 44 publications

Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment

Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment

Surface Proteoglycans as Mediators in Bacterial Pathogens Infections

Highly Efficient Multivalent 2D Nanosystems for Inhibition of Orthopoxvirus Particles

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