A supramolecular host–guest complex for heparin binding and sensing

Välimäki, Salla; Beyeh, Ngong Kodiah; Linko, Veikko; Ras, Robin H. A.; Kostiainen, Mauri A.

doi:10.1039/c8nr03132k

Cited by 33 publications

(23 citation statements)

References 57 publications

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“…Although self‐assembly systems of cavitands and polymers have been widely reported, halogen‐bonded systems are still largely unexplored . In the future studies, this XB‐based system could be further explored in several ways, for example, by adding a guest molecule to the macrocycle to increase the overall functionality or by using a more gradual solvent switch to prospectively achieve more diverse morphologies …”

Section: Methodsmentioning

confidence: 99%

Halogen‐Bond‐Mediated Self‐Assembly of Polymer–Resorcinarene Complexes

Välimäki

Gustavsson

Beyeh

et al. 2019

Macromol. Rapid Commun.

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A new supramolecular system based on halogen‐bonded macromolecular substances is presented. Binding and complex formation between a halogen bond acceptor N‐benzyl ammonium resorcinarene bromide and a library of polymeric halogen bond donors based on iodotetrafluorophenoxy functionality is shown. The complex formation was confirmed in liquid state by dynamic light scattering and transmission electron microscopy. Spectroscopic measurements in the solid state verify the halogen bonding. In particular, the study shows that both homopolymers and polyethylene glycol block copolymers act as effective halogen bond donors leading to polymer‐architecture‐dependent complex morphologies.

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Section: Methodsmentioning

confidence: 99%

Halogen‐Bond‐Mediated Self‐Assembly of Polymer–Resorcinarene Complexes

Välimäki

Gustavsson

Beyeh

et al. 2019

Macromol. Rapid Commun.

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“…The advantage of a fluorescence turn-on over a turn-off mechanism is that it requires a specific binding event to create a new signal, whereas fluorescence quenching can occur in multiple ways. Fluorescent turn-on detection could also be achieved via more exotic sensing mechanisms, such as the displacement of a quenched cationic dye from the cavity of a polycationic pillar [5]arene macrocycle, 89 the displacement of the quenched fluorescent surfen from the surface of few-layer graphene oxide, 90 or the torsional relaxation hindrance of a cationic fluorogenic ultrafast molecular rotor, 91 which led upon UFH binding to the restoration of UV absorbance or fluorescence signals.…”

Section: ■ Heparin Monitoringmentioning

confidence: 99%

Lost in (Clinical) Translation: Recent Advances in Heparin Neutralization and Monitoring

Ourri

Vial

2019

ACS Chem. Biol.

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The heparin family, which includes unfractionated heparin, low-molecular heparin and fondaparinux, is a class of drugs clinically used as intravenous blood thinner. To date, issues related to both to the reversal of anticoagulation and the blood level determination of the anticoagulant at the point-of-care remain: while the only U.S. Food and Drug Administration (FDA) approved antidote for heparin displays serious efficacy and safety drawbacks, the current assays for heparin monitoring are indirect measurements subject to their own limitations and variations. Herein, we provide an update on the numerous recent chemical approaches to tackle these issues, from which it is clear that some new antidotes and sensors for heparin certainly have the potential to exceed current clinical standards. This review aims to review a field that requires close collaborations between physicians, biologists and chemists in order to foster advances toward clinical translation. Context and challengesHeparin, which belongs to the family of glycosaminoglycans (GAGs), is a linear sulfated polysaccharide and consists of repeating disaccharide subunits of α-1,4 linked uronic acid and D-glucosamine (Figure 1). As a consequence, heparin displays the highest density of negative charges among biomacromolecules. This polyanion is widely used as an intravenous anticoagulant due to its ability to accelerate the rate at which antithrombin (AT) inhibits serine proteases within the blood coagulation cascade, most notably factor Xa and thrombin. [1][2][3][4] Polymers of various lengths such as unfractionated heparin (UFH, Mw ~ 15 kDa), low-molecular-weight heparins (LMWHs, Mw = 3.6-6.5 kDa), and the synthetic pentasaccharide fondaparinux (Mw = 1.7 kDa) are routinely delivered to patients. While UFH is used during acute thrombotic events or to maintain blood fluidity during procedures requiring extracorporeal circulation (i.e., cardio-pulmonary bypass or hemodialysis), 5,6 LMWHs and fondaparinux are prescribed to treat and/or prevent deep vein thrombosis and pulmonary embolism. 7,8 With an estimated one billion doses of heparin produced every year, heparin's market is rapidly growing, driven by the ageing of populations and the increasing incidence of cardiovascular diseases. 9 KeywordsAnticoagulants: commonly known as blood thinners, they are chemical substances that retard or inhibit the coagulation of the blood.

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“…Traditional clotting time-based assays have been proven accurate, but they are rather time-consuming. Therefore, real-time heparin detection methods would be highly desirable, and numerous luminescent, 32 colorimetric, 33,34 and fluorescent 35−38 sensors have been developed along these lines. Fluorescence-based methods have been established using both turn-on 35,37 and turn-off 36 approaches.…”

Section: Introductionmentioning

confidence: 99%

Serum Albumin–Peptide Conjugates for Simultaneous Heparin Binding and Detection

et al. 2019

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Heparin is a polysaccharide-based anticoagulant agent, which is widely used in surgery and blood transfusion. However, overdosage of heparin may cause severe side effects such as bleeding and low blood platelet count. Currently, there is only one clinically licensed antidote for heparin: protamine sulfate, which is known to provoke adverse effects. In this work, we present a stable and biocompatible alternative for protamine sulfate that is based on serum albumin, which is conjugated with a variable number of heparin-binding peptides. The heparin-binding efficiency of the conjugates was evaluated with methylene blue displacement assay, dynamic light scattering, and anti-Xa assay. We found that multivalency of the peptides played a key role in the observed heparin-binding affinity and complex formation. The conjugates had low cytotoxicity and low hemolytic activity, indicating excellent biocompatibility. Furthermore, a sensitive DNA competition assay for heparin detection was developed. The detection limit of heparin was 0.1 IU/mL, which is well below its therapeutic range (0.2–0.4 IU/mL). Such biomolecule-based systems are urgently needed for next-generation biocompatible materials capable of simultaneous heparin binding and sensing.

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A supramolecular host–guest complex for heparin binding and sensing

Cited by 33 publications

References 57 publications

Halogen‐Bond‐Mediated Self‐Assembly of Polymer–Resorcinarene Complexes

Halogen‐Bond‐Mediated Self‐Assembly of Polymer–Resorcinarene Complexes

Lost in (Clinical) Translation: Recent Advances in Heparin Neutralization and Monitoring

Serum Albumin–Peptide Conjugates for Simultaneous Heparin Binding and Detection

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