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As IO has been associated with the onset of neurodegenerative diseases (NDs), chelation therapy has been extensively used for treating IO and considered potentially suitable for NDs treatment. Desferrioxamine (DFO) presents high affinity and selectivity for iron(III), however, its clinical use as chelator is limited due to its low cell permeability. To circumvent this limitation, synthetic routes and conditions were selected for conjugating DFO to 5-aminolevulinic acid (5-ALA) or \u03b3-aminobutyric acid (GABA), non-proteinogenic amino acids previously reported as permeable to the blood\u2013brain barrier (BBB). Once obtained and purified, the conjugates 5-ALA-DFO and GABA-DFO were characterized by LC\/ESI\u2013MS and\n                    <jats:sup>1<\/jats:sup>\n                    H and\n                    <jats:sup>13<\/jats:sup>\n                    C NMR. Both exhibited iron binding abilities comparable to that of DFO, displayed identical antioxidant activity, weak interactions with human serum albumin, and were unable to remove iron from transferrin (Tf). Based on DFT calculations, a theoretical model was developed that allows to predict the efficiency of iron chelation with DFO and its conjugates, in good agreement with experimental results. In assays with human colorectal adenocarcinoma (Caco-2) cells, a model for the blood\u2013brain barrier (BBB), both chelators were non-toxic, and unlike DFO or 5-ALA-DFO, GABA-DFO was able to bind intracellular iron. Altogether, these results demonstrate that the chemical conjugation proposed here was highly effective and that GABA-DFO is a promising intracellular iron chelator.\n                  <\/jats:p>","DOI":"10.1007\/s10534-026-00841-7","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:20:26Z","timestamp":1782289226000},"page":"1921-1937","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Conjugates of desferrioxamine with 5-aminolevulinic or \u03b3-aminobutyric acid: synthesis, theoretical studies, iron-chelating ability, and penetration in human Caco-2 cells"],"prefix":"10.1007","volume":"39","author":[{"given":"Ernani","family":"Lacerda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilii D.","family":"Khripun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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