Oxygen affinity of haemoglobin is modulated by several parameters such as the allosteric effector 2-3 DPG for most mammalians. Inositol hexaphosphate (I.H.P.) exerts the same effect on haemoglobin. A previously developed new methodology for the entrapment of drugs into erythrocytes has been adapted to I.H.P.; it is based on a reversible osmotic shock. I.H.P. loaded red blood cells have characteristics very similar to those of native cells. The decrease in oxygen affinity is related to the dose of encapsulated I.H.P. In piglets, transfusion of such cells has led to an increase of oxygen extraction from haemoglobin. Normal anesthetized animals regulate their oxygen consumption by reduction of cardiac output.
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Nat Chem
January 2025
Institute of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
University of Amsterdam Van 't Hoff Institute for Molecular Sciences: Universiteit van Amsterdam Van 't Hoff Institute for Molecular Sciences, HIMS, NETHERLANDS, KINGDOM OF THE.
The complexity of allosteric enzymatic regulation continues to inspire synthetic chemists seeking to emulate interconnected biological systems. In this work, a Pt2L4 cage capable of catalyzing the cyclization reaction of an alkynoic tosyl amide is orthogonally coupled to a diacid-catalyzed carbodiimide-hydration cycle. This new Pt-catalyzed cyclization reaction is demonstrated to exhibit electronic regulation by inclusion of different guest effectors.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Centre for Molecular Biophysics, UPR CNRS 4301, Orleans, France.
The hypoxic microenvironment is crucial for tumour cell growth and invasiveness. Tumour tissue results from adaptation to reduced oxygen availability. Hypoxia first activates pro-angiogenic signals for alleviation.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Biochemistry, University of Zurich, Winterthurerstrass 190, 8057 Zurich, Switzerland.
Type III clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems (type III CRISPR-Cas systems) use guide RNAs to recognize RNA transcripts of foreign genetic elements, which triggers the generation of cyclic oligoadenylate (cOA) second messengers by the Cas10 subunit of the type III effector complex. In turn, cOAs bind and activate ancillary effector proteins to reinforce the host immune response. Type III systems utilize distinct cOAs, including cyclic tri- (cA3), tetra- (cA4) and hexa-adenylates (cA6).
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.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!