The application of solid-state (SS) nanopore devices to single-molecule nucleic acid sequencing has been challenging. Thus, the early successes in applying SS nanopore devices to the more difficult class of biopolymer, glycosaminoglycans (GAGs), have been surprising, motivating us to examine the potential use of an SS nanopore to analyze synthetic heparan sulfate GAG chains of controlled composition and sequence prepared through a promising, recently developed chemoenzymatic route. A minimal representation of the nanopore data, using only signal magnitude and duration, revealed, by eye and image recognition algorithms, clear differences between the signals generated by four synthetic GAGs. By subsequent machine learning, it was possible to determine disaccharide and even monosaccharide composition of these four synthetic GAGs using as few as 500 events, corresponding to a zeptomole of sample. These data suggest that ultrasensitive GAG analysis may be possible using SS nanopore detection and well-characterized molecular training sets.
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http://dx.doi.org/10.1073/pnas.2022806118 | DOI Listing |
Bioorg Med Chem
December 2024
Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, via G. Colombo 81, 20133 Milano, Italy.
Molecules
December 2024
School of Chemical and Physical Sciences and Centre for Glycoscience, Keele University, Keele, Staffordshire ST5 5BG, UK.
Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is a key regulator of biological processes. Owing to the inherent structural complexity of HS, structure-to-function studies with its ligands are required, and materials to improve the understanding of such interactions are therefore of high importance. Herein, the synthesis of novel -linked GlcN-α(1→4)-GlcA disaccharide building blocks is detailed.
View Article and Find Full Text PDFGlycoconj J
December 2024
Departments of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
Dengue viruses (DENV) are transmitted to humans through mosquito bites and infect millions globally. DENV uses heparan sulfate (HS) for attachment and cell entry by binding the envelope protein to highly sulfated HS on target cells. Therefore, inhibiting the binding between DENV and HS could be a promising strategy for preventing DENV infection.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Medical Biochemistry and Microbiology, The Biomedical Center, Uppsala University, Uppsala, 75123, Sweden.
The high transmissibility and mutation ability of coronaviruses enable them to easily escape existing immune protection and also pose a challenge to existing antiviral drugs. Moreover, drugs only targeting viruses cannot always attenuate the "cytokine storm". Herein, a synthetic heparan sulfate (HS) mimetic, HMSA-06 is reported, that exhibited antiviral activities against both the SARS-CoV-2 prototype and Omicron strains by targeting viral entry and replication.
View Article and Find Full Text PDFBiomater Adv
October 2023
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore; Department of Orthopaedic Surgery, Yong Yoo Lin School of Medicine, National University of Singapore; School of Chemical Engineering, The University of Queensland, Brisbane, Qld 4072, Australia. Electronic address:
Bone morphogenetic protein 2 (BMP-2) is an osteoinductive protein and a potent inducers of bone formation, playing an essential role during bone fracture repair. Heparan sulfate (HS), a highly charged and linear polysaccharide, is known to interact with and enhance BMP-2 bioactivity. Despite showing potential as a potent adjuvant of the endogenous bone healing response, commercially available HS is derived from animal sources which are less desirable when considering translation into the clinic.
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