20.500.12556/RUL-177836 α-Aminoboronic acid moieties in boro dipeptides modulate proteasome subunit selectivity and provide access to compounds with potent anticancer and anti-inflammatory activity Proteasomes regulate cellular protein homeostasis and are key targets in treating cancer, inflammation, and autoimmune diseases. The two main forms, the constitutive proteasome and immunoproteasome, each contain three catalytically active subunits with distinct substrate specificities. The first approved proteasome inhibitor, bortezomib, is nonselective and causes dose-limiting toxicity. Herein, we report dipeptide boronic acids with varying P1 residues, prepared using our recently developed method for α-aminoboronic acids formation. Most compounds inhibited various immuno/proteasome subunits in the low nanomolar range, displaying inhibition profiles distinct from bortezomib, ranging from β5i/β1i-selective to β5c/β5i-directed inhibitors. Although their cytotoxicity to cancer cells was not improved compared to bortezomib, selected compounds proved less toxic to noncancer cells and with anti-inflammatory activity comparable to that of zetomipzomib (KZR-616). The presented boro dipeptides with tailored P1 residues provide a basis for designing subunit-selective compounds with boronic acid as the warhead and optimized P2 and/or P3 positions. proteasomes homeostasis cellular proteins anticancer activity anti-inflammatory activities cells inhibition inhibitors peptides proteins screening assays proteasomi homeostaza celične beljakovine antikancerogeno delovanje protivnetno delovanje farmacevtska kemija citologija celična fiziologija antionkogeni protivnetna zdravila true false true Angleški jezik Slovenski jezik Članek v reviji 2026-01-09 09:17:10 2026-01-09 09:17:15 2026-01-10 04:27:53 0000-00-00 00:00:00 2025 0 0 Str. 26405−26417 iss. 24 Vol. 68 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 543.2/.9 1520-4804 10.1021/acs.jmedchem.5c02548 260217091 α-aminoboronic-acid-moieties-in-boro-dipeptides-modulate-proteasome-subunit-selectivity-and-provide-access-to-compounds.pdf α-aminoboronic-acid-moieties-in-boro-dipeptides-modulate-proteasome-subunit-selectivity-and-provide-access-to-compounds.pdf 1 1E9D1F9D12D18D032B5808BADF8CFCC4 5ff8656488e51ccdcaf776083f3d968f6cc68557a7bba802cdd644fc31ec9183 95a0605b-ed6d-11f0-bf92-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=225237 https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c02548 1 990ba52d-ed33-11f0-bf92-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=225183 Fakulteta za farmacijo 0 0 0