The production of hyperpolymer haemoglobins, exhibiting sufficiently low colloid osmotic pressure and sufficiently low viscosity is possible, even in concentrations, and therewith oxygen transport capacity, high enough to supply an organism adequately with oxygen. Such hyperpolymers, when infused, are tolerated by anaesthetized rats in acute blood exchange experiments. Ex vivo determinations of plasma colloid osmotic pressure and both, plasma and whole blood kinematic viscosity during blood exchange showed, that corresponding properties found in vivo were refound within the animal. Furthermore we could show that hyperpolymers produced from desoxygenated human haemoglobin with divinyl sulfone as a crosslinker take part in tissue supply of oxygen to a substantial degree (about 50%) without and with increased inspiratory oxygen fraction, demonstrating the principal ability of hyperpolymers to transport oxygen in blood and to deliver it to tissues.
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http://dx.doi.org/10.1007/978-1-4615-2468-7_27 | DOI Listing |
Nat Commun
January 2025
Department of Electrical and Electronic Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Elife
December 2024
Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: (1) primary sulfonamide group recognizing carbonic anhydrases (CA), (2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and (3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification.
View Article and Find Full Text PDFBioorg Med Chem Lett
March 2025
Kazan Federal University, Kazan, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
The NRF2 transcriptional factor is a member of cellular stress response machinery and is activated in response to oxidative stress caused either by cellular homeostasis imbalance or by environmental challenges. NRF2 levels are stringently controlled by rapid and continuous proteasomal degradation. KEAP1 is a specific NRF2 binding protein that acts as a bridge between NRF2 and the E3 ligase Cullin-3.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India. Electronic address:
Gelatin hydrogels have drawn attention for their diverse biomedical applications due to their flexible physiochemical properties. However, such gelatin hydrogels are made of toxic crosslinkers and photoinitiators, restricting their non-invasive deep tissue application. The in-situ forming chemical crosslinked without such toxic crosslinker and UV light has not been explored under physiological conditions.
View Article and Find Full Text PDFSci Rep
November 2024
Global CMC Development, Global R&D, Sanofi, 350 Water Street, MA 02141, Cambridge, USA.
Applications of functionalized hyaluronic acid (HA) hydrogels for numerous biomedical applications requires their detailed structural characterization. Since these materials are prepared by multistep chemical modifications in the solid phase and not amenable to characterization by standard analytical tools, we employed high-resolution solid-state NMR spectroscopy to gain detailed insights into the structures of the functionalized HA hydrogels. Divinyl sulfone crosslinked HA hydrogels were converted into maleimide-functionalized hydrogels, which were subjected to chemoselective thiol-maleimide reaction using L-cysteine as the protein mimetic thiol reagent.
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