Heparin is an anionic polysaccharide widely used in clinics as an anticoagulant. However, heparin usage requires an antidote and sensors for safe operation during and after surgeries. In this study, a host-guest complex capable of selective heparin binding and sensing is presented. Heparin binding affinity was studied in solution with a variety of polycationic macrocyclic hosts, a pillar[5]arene and multiple resorcin[4]arenes, by dynamic light scattering, dye displacement assay, isothermal titration calorimetry, and anti-Xa assay. The measurements reveal the significant importance of multivalency in electrostatic host-heparin binding in competitive, application-relevant media. Additionally, to monitor the heparin concentration, a host-guest indicator displacement assay was performed by following the free and bound state of the methyl orange dye in UV-Vis spectroscopic experiments. Furthermore, this colorimetric sensing based on the tertiary host-guest-heparin supramolecular assembly was utilized in the construction of a calibration curve in a range of blood plasma concentrations.
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http://dx.doi.org/10.1039/c8nr03132k | DOI Listing |
Macromol Biosci
January 2025
Heinrich- Heine- University Düsseldorf, Faculty of Mathematics and Natural Sciences, Institute of Organic Chemistry and Macromolecular Chemistry, 40204, Düsseldorf, Germany.
Glycosaminoglycans (GAGs) play a pivotal role in pathogen attachment and entry into host cells, where the interaction with GAGs is critical for a diverse range of bacteria and viruses. This study focuses on elucidating the specific interactions between sulfated GAGs and the adhesin OmcB (Outer membrane complex protein B) of Chlamydia species, examining how structural characteristics of GAGs, such as sulfation degree and molecular weight, influence their binding affinity and thereby affect bacterial infectivity. A surface-based binding assay is established to determine the binding constants of OmcB with various GAGs.
View Article and Find Full Text PDFJ Trop Med
January 2025
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Laboratory of Parasite and Vector Biology, Ministry of Public Health, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China.
Glycosaminoglycan (GAG) molecules on the surface of red blood cells play an important regulatory role in the invasion of merozoites of apicomplexan protozoa. Heparan sulfate, a type of GAG molecule, has been identified as an important receptor facilitating the invasion of red blood cells by these parasites. Proteins in the parasite that exhibit strong affinity for heparin may play a pivotal role in this invasion process.
View Article and Find Full Text PDFACS Omega
January 2025
Institute of Chemical Process Fundamentals Czech Academy of Sciences, Rozvojová 135, Prague 165 02, Czech Republic.
Efficient and safe carriers of genetic material are crucial for advancing gene therapy. Three new series of cationic dendritic nanocarriers based on a carbosilane scaffold, differentiated by peripheral modifications: saccharide (CS-glyco), amine (CS-N), and phosphonium dendrimers (CS-P) were designed for binding, protecting, and releasing polyanionic compounds like therapeutic siRNA. Besides introducing synthetic methodology, this study brings a unique direct interstructural comparison of 16 dendritic nanovector's characteristics, addressing a gap in typical research that focuses on uniform structural types.
View Article and Find Full Text PDFAntimicrob Agents Chemother
January 2025
Department of Pharmacy Practice, College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA.
Vancomycin causes kidney injury by accumulating in the proximal tubule, likely mediated by megalin uptake. Protamine is a putative megalin inhibitor that shares binding sites with heparin and is approved for the treatment of heparin overdose. We employed a well-characterized Sprague-Dawley rat model to assess kidney injury and function in animals that received vancomycin, protamine alone, or vancomycin plus protamine over 5 days.
View Article and Find Full Text PDFBiochem Biophys Rep
March 2025
Genis hf, Reykjavik, Iceland.
The chitinase-like protein YKL-40 (CHI3L1) has been implicated in the pathophysiology of inflammation and cancer. Recent studies highlight the growing interest in targeting and blocking the activity of YKL-40 to treat cancer. Some of those targeting-strategies have been developed to directly block the heparin-affinity of YKL-40 with promising results.
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