Serum Albumin-Peptide Conjugates for Simultaneous Heparin Binding and Detection

Qing Liu; Salla Välimäki; Ahmed Shaukat; Boxuan Shen; Veikko Linko; Mauri A Kostiainen

doi:10.1021/acsomega.9b02883

Serum Albumin-Peptide Conjugates for Simultaneous Heparin Binding and Detection

ACS Omega. 2019 Dec 10;4(26):21891-21899. doi: 10.1021/acsomega.9b02883. eCollection 2019 Dec 24.

Authors

Qing Liu¹, Salla Välimäki¹, Ahmed Shaukat¹, Boxuan Shen¹, Veikko Linko¹, Mauri A Kostiainen¹

Affiliation

¹ Biohybrid Materials, Department of Bioproducts and Biosystems and HYBER Center of Excellence, Department of Applied Physics, Aalto University, 00076 Aalto, Finland.

Abstract

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.