9tnr

L12 G-quadruplex-forming aptamer targeting HMGB1 protein

spinqualitylabelsall models 9tnr Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9tnr is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed High Mobility Group Box 1 (HMGB1) is a valuable therapeutic target in inflammatory, autoimmune diseases, and cancer. Recently, some of us identified a set of anti-HMGB1 aptamers, folding into G-quadruplex structures of different topology. Among them, L12 and L41 were the most effective aptamers as for affinity and activity towards the protein. Here, nuclear magnetic resonance (NMR) spectroscopy, corroborated by size exclusion high performance liquid chromatography (SE-HPLC) and circular dichroism (CD), allowed defining the structural features of L12 and L41. In-depth structural details were obtained for the monomeric forms of these aptamers in a K(+)-rich (100 mM K(+)) buffer, mimicking the intracellular environment. Under these conditions, both L12 and L41 folded in hybrid G-quadruplex structures. By cross-referencing the obtained data, we inferred that these structures were also the main monomeric folded species in the Na(+)-rich Phosphate Buffered Saline (PBS) buffer, mimicking the extracellular environment, suggesting that these aptamers share similar recognition patterns when interacting with the target protein. However, in PBS a higher amount of hybrid-2 G-quadruplex was observed for L12 than L41. Biolayer interferometry (BLI) analysis demonstrated a preference of HMGB1 for L12 over L41, in line with in vitro assays, showing higher ability to inhibit the HMGB1-induced cell migration for L12 than L41. These findings suggest that HMGB1 recognizes the hybrid-2 G-quadruplex folding of these aptamers, present in higher degree in L12 than L41. In summary, this work provides precious insights into the conformational preferences of L12 and L41, of crucial importance to design more effective HMGB1 inhibitors. Unraveling the NMR structures of G-quadruplex-forming aptamers acting as inhibitors of High Mobility Group Box 1 (HMGB1) pathological activity.,Trajkovski M, Platella C, Musumeci D, Napolitano E, Esposito CL, Catuogno S, Plavec J, Montesarchio D Int J Biol Macromol. 2026 Mar 24;357:151585. doi: 10.1016/j.ijbiomac.2026.151585. PMID:41881226 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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