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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Virus capsid proteins modified with a heparin binding peptide can selectively bind and encapsulate heparin inside a protein cage.

Figure 4. Dissipative DNA assemblies fueled by redox reactions. A) Left panel: The reversible release of a ligand from a DNA sequence fueled by a redox reaction. Right panel: The fluorescence evolution upon the repeated addition of the disulfide-linked DNA modulator. Reproduced with permission. [36] Copyright 2020, Wiley-VCH. B) Top left panel: Schematic illustration of the transient self-assembly of DNA nanotubes activated by disulfide-containing DNA. Top middle panel: The measured DNT formation in the presence of disulfide activators with various lengths at 1 and 24 h. Top right panel: Fluorescence microscopy images of transient DNA nanotubes in the presence of Act_16. Bottom left panel: Schematic illustration of the transient selfassembly of DNA nanotubes inhibited by disulfide-containing DNA. Bottom middle panel: The measured DNA nanotube formation in the presence of disulfide inhibitors with various lengths at 1 and 24 h. Bottom right panel: Fluorescence microscopy images of transient DNA nanotubes in the presence of Inhib_14. Reproduced with permission. [37] Copyright 2020, Wiley-VCH.