Heparin sensing and binding – taking supramolecular chemistry towards clinical applications

Abstract

Heparin is a vital biomolecule in widespread clinical use as an anti-coagulant. Heparin sensors have potential applications in the bedside detection of heparin levels in human blood during surgery, while high-affinity heparin binders may enable the development of effective heparin reversal agents for use in patients once surgery is complete. However, human blood is a challenging medium in which to achieve selective high-affinity molecular recognition, and as such, this system provides a fascinating challenge to supramolecular chemists. This has encouraged research using a variety of different systems and is stimulating new approaches to the application of molecular recognition. This review article provides an overview of research from both clinical and supramolecular communities towards heparin binding and sensing and considers how this area may develop in the future.

Pharmacology of Heparin and Related Drugs

“…Earlier methods have Pharmacology of Heparin and Related Drugs relied on prior removal of heparin from the biologic medium using precipitation, cation exchange chromatography (Jaques et al, 1990), or immobilized polylysine (Mohammad et al, 1980). Heparin sensors have recently been reviewed (Bromfield et al, 2013b). A sensor capable of quantitative response to heparin in therapeutic concentrations in plasma has been a goal of many research groups in the past few decades.…”

“…A sensor capable of quantitative response to heparin in therapeutic concentrations in plasma has been a goal of many research groups in the past few decades. Problems of ionic strength and autofluorescence have hampered the achievement of sufficiently high sensitivity (Bromfield et al, 2013b). Researchers devised a polyion-sensitive membrane electrode that is capable of estimating heparin concentration in blood by potentiometric titration with protamine (Ramamurthy et al, 1998(Ramamurthy et al, , 1999.…”

Emergence of highly-ordered hierarchical nanoscale aggregates on electrostatic binding of self-assembled multivalent (SAMul) cationic micelles with polyanionic heparin

“…Given the potential clinical relevance of self-assembled nanostructures for heparin binding and reversal, 9 we considered it of great importance to verify whether the highly ordered hierarchical nanoscale aggregates revealed by TEM for C14-DAPMA and C16-DAPMA are preserved in solution. To the purpose, Dissipative Particle Dynamics (DPD) simulations 8,15b,18 were initially employed to predict the self-assembly and spatial organization of these two amphiphiles in solution in presence of heparin (Figure 2).…”

“…Our own research has focused on the development of low-molecular-weight building blocks which form self-assembled multivalent (SAMul) heparin binders such systems have advantages for coagulation control in terms of synthetic simplicity and tunability, high activity as a result of mulltivalent binding and pharmaceutically-useful degradation and disassembly profiles. 8 Given the clinical importance of heparin binding, 9 it is vital to understand the self-assembly and binding mechanisms inherent in this SAMul approach.…”

Morphological control of self-assembled multivalent (SAMul) heparin binding in highly competitive media

“…5 There has been general interest in binding polyanions using colloidal polycations. 6 Self-assembled nanoscale systems such as liposomes have been used to bind heparin, primarily with the goal of enhancing liposome biocompatibility.…”